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Summary

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Postoperative pain is an important clinical problem that has received increasing attention in recent years. However, pain following craniotomy has been a comparatively neglected topic; this review seeks to redress this imbalance. A brief overview of the anatomy of the skull and its linings is given, with particular reference to innervation. The various approaches for craniotomies are classified, with their association with acute and long-term effects on analgesic requirements. A comprehensive search of the literature was undertaken to ascertain the incidence of acute pain post craniotomy and current thoughts on pharmacological management, touching briefly on pre-emptive treatment. Also discussed is the much neglected but nevertheless real incidence of chronic pain following craniotomy and its underlying pathogenesis, prevention and treatment.

Postoperative pain is an important clinical problem that has received much attention in recent years. Anaesthetists today pride themselves on keeping their patients pain-free. Nonetheless, it was not until 1996 when De Benedettis et al. [1] undertook a pilot study to assess postoperative pain in neurosurgery that the incidence, magnitude, and duration of acute pain experienced by neurosurgical patients was quantified.

This review begins with a brief overview of the anatomy of the skull and its linings, with particular reference to innervation. The various approaches for craniotomies are classified, with their association with acute and long-term effects on analgesic requirements. A comprehensive search of the literature was undertaken to ascertain the incidence of acute pain post craniotomy and current thoughts on pharmacological treatment, touching briefly upon pre-emptive treatment. The final section is directed towards the much neglected but nevertheless real incidence of chronic pain following craniotomy and discusses its underlying pathogenesis, prevention and treatment.

Anatomy and innervation of the skull and its linings

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

The skull is a highly intricate part of the axial skeleton and its role is by no means restricted to being protective. Protection of the brain from potentially damaging external impacts is of undoubted value, but the skull also isolates the cerebral circulation, as well as allowing the meninges and their contained fluids to work as effective buffers.

Osteology

The upper part of the cranium forms a box to enclose and protect the brain; it is often termed the calvaria. The remainder of the skull forms the facial skeleton, of which the lower part is the freely moveable mandible. The region of the forehead is formed by the frontal bone, which passes backwards in the vault of the skull up to the coronal suture, where it meets the right and left parietal bones. These two bones make up most of the cranial vault and articulate with each other at the sagittal suture. They extend posteriorly to the occipital bone, all three bones meeting at the lambdoid suture.

When the skullcap or calva is removed, the base of the skull is exposed. It shows a natural division into three regions: anterior, middle and posterior cranial fossae. The inferior surface of the base of the skull is very irregular and exhibits a number of important foramina through which exit the brain stem, cranial nerves and blood vessels.

The scalp

The interior of the cranium is lined with a fibrous membrane, the endocranium, which is the outer zone of the dura mater. It becomes continuous with the periosteum on the outer surface of the skull, the pericranium. The epicranial musculature consists of two main parts: occipitofrontalis and temporoparietalis. The galea aponeurotica covers the upper part of the cranium and forms with the epicranius a continuous fibromuscular sheet extending from the occiput to the eyebrows. The scalp thus consists of five layers: skin, subcutaneous tissue, epicranium, subaponeurotic areolar tissue and the pericranium.

The meninges

The brain is enveloped by three membranes or meninges: the dura mater, the arachnoid and the pia mater. The cerebral dura mater lines the interior of the skull and forms both an internal periosteal layer and a supporting membrane for the brain. The supporting role of the dura is evident in that it forms the falx cerebri and cerebelli, tentorium cerebelli and diaphragm sellae.

Innervation [2]

Innervation of the scalp and the dura involves a rich plexus, arising from:

  • •  
    the trigeminal nerve, including its ganglion, the three principal divisions and their branches;
  • •  
    the upper three cervical nerves;
  • •  
    the cervical sympathetic trunk;
  • •  
    minor branches from the vagus;
  • •  
    minor branches from the hypoglossus;
  • •  
    some twigs from the facial and glossopharyngeal nerves.

Surgical approaches in craniotomy

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Craniotomy is the surgical opening of the cranium. Various approaches can be taken depending upon the indication for surgery. Surgical approaches to the skull have been developed, refined and modified to provide the best possible exposure with the least associated morbidity for the patient.

Craniotomy may be supratentorial or infratentorial, or occasionally a combination of both (Fig. 1). Infratentorial craniotomy is better known by the term skull base surgery. Tables 1–3 show the various approaches used to expose the cranial fossa and associated surgical indications.

image

Figure 1. Combined supra- and infratentorial approach.

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Table 1.  Supratentorial craniotomy approaches and procedures.
Supratentorial approachesIndications
FrontalClip ligation of aneurysm
FrontotemporalResection of arteriovenous malformation
TemporalResection of glioma or other tumour
PterionalResection of convexity meningioma
 Temporal lobectomy
Evacuation of acute subdural haematoma
Table 2.  Classical approaches to base of skull surgery.
ApproachCranial fossa exposedIndications
CraniofacialAnterior cranial fossaElevation or resection of the frontal lobe,  osteotomy of skull base
OrbitocranialAnterior cranial fossaElevation of frontal and/or temporal lobes
InfratemporalMiddle cranial fossaDecompression/mobilization of the facial nerve
Suboccipital  or transcondylarPosterior cranial fossaOccipital condylectomy, mastoidectomy,  resection of C1 – C3 vertebral body,  decompression of the vertebral artery,  decompression of herniated tonsils
Table 3.  Lateral approaches in skull base surgery.
ApproachCranial fossa exposedIndications
RetrosigmoidPosterior cranial fossaDecompression of sigmoid sulcus, or  facial nerve, acoustic neuroma excision
TranslabyrinthinePosterior cranial fossaLabyrinthectomy, excision of acoustic neuroma
Orbitocranial zygomaticMiddle cranial fossaExtra or Intradural elevation of temporal lobe

Incidence of acute pain post craniotomy

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Craniotomies are generally thought to be less painful than other operations [3], but this assumption has been challenged [1, 4, 5]. In their pilot study published in 1996, De Benedettis et al. [1] showed that postoperative pain was more common than generally assumed, quoting a figure of 60%. In two-thirds of these patients, the intensity of pain was moderate to severe. Pain most frequently occurred within the first 48 h after surgery, but up to 32% of patients still endured pain after this initial period. While craniotomy pain may be less severe than pain after other operations, there is a growing consensus that it remains under-treated in the acute recovery phase for at least a minority of patients [1, 3, 5].

The quality of pain is normally described as pulsating or pounding akin to ‘tension headaches’. Less frequently, it is described as steady and continuous. Female and younger patients show the highest incidence of pain, in keeping with previous studies [6, 7]. Women report higher rates of pain than men, possibly because of greater health awareness, pain role perception and illness orientation. Older people are generally thought to be relatively tolerant of pain.

Gee et al. [8] attempted to evaluate any difference between the pre-existing pathology, including pre-operative headache. They studied patients who underwent craniotomy for resection of brain tumour, intractable epilepsy or intracranial haemorrhage. Half of the patients had not reported any pre-operative headache, yet one-fifth of these reported significant headache postoperatively. Interestingly, most these underwent surgery for intractable epilepsy. They concluded that in the acute postoperative state, the characteristics of the headache suggest a combination of tension type and ‘site of injury’ headache overlying the surgical site. The nature of the headaches was similar to post-traumatic headaches.

On a similar note, Pfund et al. [9] analysed the incidence of pre-operative and postoperative pain in 279 patients undergoing craniotomy for resection of brain tumour. They demonstrated that only 164 of these patients had reported any pre-operative headaches. Headaches were more common in patients with metastatic brain tumours and astrocytomas, as well as those with tumours localised in the infratentorial space or ventricles. Although they concluded that chronic headache might not necessarily be a manifestation of the presence or recurrence of tumour, a significant change in the type of headache associated with new abnormal neurological signs should be seen as an indication of possible recurrence until proven otherwise.

It is commonly recognised that the degree of postoperative pain following craniotomy depends on the type of surgical approach. Base of skull surgery, particularly that used for posterior fossa tumours and acoustic neuromas, is associated with a higher incidence of disabling postoperative headache. Vijayan [10] showed that 42% of patients awaiting surgery for excision of acoustic neuroma had only minor or no headaches prior to surgery. After surgery, 75% of patients experienced headache. A very gradual improvement of the pain occurred in 32% of those patients over time.

Pathogenesis of pain post craniotomy

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Pain is described as prominently superficial in the majority of patients [1], suggesting a somatic rather than a visceral origin. The pain is thought to arise from pericranial muscle and soft tissue. Suboccipital and subtemporal routes are associated with the highest incidence of pain, possibly related to surgical stress in major muscle tissues, i.e. the temporal, splenium capitis and cervicis muscles. The pain that results is typically nociceptive in nature and is secondary to the surgical incision and reflection of the muscle underlying the scalp. Pain is not thought to arise from the brain tissue itself [1, 3, 11].

Role of neurotransmitters in the pathogenesis of headache

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Recent evidence [12, 13] suggests that surgical incision and other noxious peri-operative events may induce prolonged changes in central neural function that will later contribute to postoperative pain.

The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The pain perceived, moreover, is assumed to be directly proportional to the extent of the injury. Recent research, as we have already stated, indicates far more complex mechanisms. Clinical and experimental evidence shows that noxious stimuli may sensitise central neural structures involved in pain perception. Experimental evidence of these changes is illustrated by the development of sensitisation, wind-up or expansion of receptive fields of CNS neurones, as well as by the enhancement of flexion reflexes and the persistence of pain or hyperalgesia after inputs from injured tissues are blocked.

It is clear that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but is rather a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioural output is significantly influenced by the ‘memory’ of these prior events.

The transmission of pain from the periphery to the cortex depends on integration and signal processing within the spinal cord, brainstem, and forebrain.

Sensitisation, a component of persistent or chronic pain, may develop either through peripheral mechanisms or as a consequence of altered physiology in the spinal cord or forebrain. Several molecular and biophysical mechanisms [14, 15] contribute to the phenomenon of sensitisation and persistent pain, including up-regulation of sensory neurone-specific sodium channels and vanilloid receptors, phenotypic switching of large myelinated axons, sprouting within the dorsal horn, and loss of inhibitory neurones due to apoptotic cell death. Recently, forebrain structures have been implicated in the pathophysiology of persistent pain.

Wind-up is a frequency-dependent increase in the excitability of spinal cord neurones evoked by electrical stimulation of afferent C-fibres. Although it has been studied for the past 30 years, there are still uncertainties about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors [15]. However, most drugs capable of reducing the excitability of spinal cord neurones, including opioids and non-steroidal anti-inflammatory drugs, can also reduce or even abolish wind-up.

Other theories involving synaptic efficacy, potassium channels, calcium channels, etc., have also been proposed for the generation of this phenomenon. Whatever the mechanisms involved in its generation, wind-up has been interpreted as a system for the amplification in the spinal cord of the nociceptive message that arrives from peripheral nociceptors connected to C-fibres. This probably reflects the physiological system activated in the spinal cord after an intense or persistent barrage of afferent nociceptive impulses. On the other hand, wind-up, central sensitisation and hyperalgesia are not the same phenomenon, although they may share common properties.

In patients with chronic tension type and migraine-like headaches, including those associated with head injury, it is postulated that the serotonergic system may be disturbed. Evidence suggests that stimulation of GABA receptors in the raphe nuclei decreases the firing rate of serotonergic neurones. Post-traumatic headaches manifesting as ‘migraine-like’ in particular [16] are thought to be a problem of central neuronal hyperexcitability caused by increased activity of excitatory amino acids, which leads to a spreading depression of neuronal activity.

In an analysis of 54 journal articles, Marcus [17] concluded that serotonin plays an important role in the pathogenesis of headache. Abnormalities in blood vessels have traditionally been implicated in the pathogenesis of migraine headaches, and excessive muscle contraction in tension type headaches. It is thought that changes in serotonin may precede these changes.

Studies by Cavallotti et al. [18, 19] have also revealed that there are catecholaminergic nerve fibres present in human cranial dura mater. The basal region is more richly innervated than the calvarial region. Moreover, these nerve fibres are more abundant in the perivascular dural zone than in the intervascular zone. It is hypothesised that these catecholaminergic nerve fibres may be involved in headache.

An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.

Pre-emption of pain

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

In 1988, Wall [20] proposed the concept of pre-emptive analgesia and suggested that ‘we should consider the possibility that pre-emptive pre-operative analgesia has prolonged effects which long outlast the presence of drugs’. The basis for his assumption was the increasing evidence [21, 22] suggesting that the development of chronic pain is related to central neuroplasticity. It is now well recognised [22, 23] that severe or prolonged acute pain in the postoperative period as well as post surgical complications, commonly leading to increased nociception, are significant predictors for the development of chronic pain. This is an important argument in favour of good and aggressive management of acute pain after surgery. It would not only prevent unnecessary suffering of patients, but might also decrease the incidence of chronic pain states.

Treatment of acute pain

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

In 1995, 97% of Consultant members of the Neuroanaesthesia Society of Great Britain and Ireland used intramuscular codeine phosphate for postoperative analgesia in neurosurgery [24], even though more than half of them felt that this provided inadequate analgesia. Despite these findings, only 3% of those surveyed said that they would use other opioids postoperatively because of fears about respiratory depression and sedation. Since then, several authors have advocated the reappraisal of the attitude to treatment of acute pain after craniotomy, and encouraged the use of combined modalities of pain relief; infiltration with local anaesthetics, non-steroidal anti-inflammatory drugs and the use of patient controlled opioid analgesia (see Table 4).

Table 4.  Level of evidence for various modalities of pain relief in neurosurgery.
InterventionSourceLevel of evidence
Traditional thought that there is minimal  postoperative pain is challengedDunbar et al.[4]II-3
Quiney et al. [5]II-2
De Benedittis et al. [1]II-2
Stoneham & Walters [24]I
Postoperative analgesic recommendations have  been very conservative, intramuscular  codeine being the most commonly usedMacKersie [39]III
Stoneham & Walters [24]I
Codeine has been shown to be superior to  tramadol as a postop analgesic and not  significantly different from i.v.  PCA morphineStoneham & Walters [24]I
NSAIDS may be contraindicated in some  settings due to concerns regarding  intracranial bleedingPalmer et al. [35]II-2
PCA morphine is more effective than codeine  in providing pain relief, and has been safely  used without any respiratory depressionGoldsack et al. [33]II
Stoneham et al. [30]II
Scott Jellish et al. [31]III
Infiltration of the scalp with bupivacaine  helps to achieve pain control in the  immediate postoperative periodBloomfield et al. [25]I

Infiltration with local anaesthetic

Scalp infiltration with 0.25% bupivacaine with 1 : 200 000 epinephrine has been shown to reduce immediate pain postoperatively [25]. Furthermore, when 0.75% ropivacaine was used for infiltration, pain relief can last up to 48 h postoperatively. This may be related to a pre-emptive mechanism of pain relief [26].

Use of paracetamol and codeine

For non-ventilated patients in the immediate postoperative period appropriate analgesia consists of oral, rectal or intramuscular codeine phosphate, 30–60 mg 4-hourly. Codeine [27, 28] has been traditionally the opiate of choice because it has a ceiling to its respiratory depressant effects and it does not mask pupillary signs. Paracetamol 1 g 6-hourly will give a synergistic effect with the codeine.

Following absorption, codeine undergoes extensive metabolism, up to 15% undergoing demethylation with a cytochrome P450 enzyme to form morphine. The variable effect of codeine is the result of the great variability of the P450 gene. Thus some patients in whom the cytochrome P450 gene encoding contains inactivating mutations are poor metabolisers. They have a severely compromised ability to metabolise certain drugs, including codeine.

The traditional use of codeine has recently been questioned [29]. A series of articles by Stoneham and Walters [5, 24, 30] demonstrated inadequate analgesia with codeine in adults and they recommend the use of patient controlled analgesia with morphine as a better alternative.

Patient controlled analgesia with morphine

Scott Jellish et al. [31] report that they have found that patient controlled analgesia is subjectively better and leads to overall lower opioid requirement. It provides a mechanism to titrate drug administration, allowing the patient to exert control over their pain management. This may, in turn, alleviate the psychological stress, which is aggravated by pain. Their experience over 2 years using a dosing regimen of 1.5 mg morphine with a lockout period of 8 min was associated with no incidence of respiratory depression or re-intubation. They recommend that the total dose in 4 h should not exceed 40 mg. They routinely combine ondansetron with patient controlled morphine and consistently achieve higher satisfaction in terms of both analgesia and control of nausea and vomiting [32].

Similarly, Stoneham et al. [30] performed a prospective randomised trial comparing intramuscular codeine with patient controlled analgesia using morphine 1 mg bolus with a 10-min lockout and no background infusion. Their results only elicited a small non-significant reduction in pain scores in the patient controlled analgesia group, but again there were no adverse effects associated with the use of morphine.

Intramuscular morphine

Goldsack et al. [33] compared the use of 10 mg intramuscular morphine and 60 mg of intramuscular codeine in a double-blind trial. They concluded that morphine was more effective than codeine in terms of pain relief, fewer doses of morphine than codeine were required, and none of their patients exhibited any form or respiratory depression, sedation, pupillary constriction or unwanted cardiovascular effects.

Opioid agonist/antagonist drugs such as buprenorphine have no particular advantage over codeine or morphine [34]. In ventilated patients, opiates should be used with greater caution so as not to delay weaning from mechanical ventilation.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs may enhance analgesia and reduce the postoperative opioid consumption. Diclofenac 100 mg rectally may be used every 18 h if there is no bleeding problem or renal insufficiency. NSAIDs should, however, be used with caution; there is always the risk, albeit small, of postoperative haematoma formation as a result of their effect on platelet function.

Palmer et al. [35] published a 5-year retrospective study of around 7000 craniotomies. Of these, 1.1% required postoperative surgical evacuation of a haematoma. Risk factors were present in two-thirds of the patients. Administration of antiplatelet agents (aspirin and NSAIDs) was the most commonly associated risk factor. They are also the most common cause of postoperative renal failure. Renal blood flow can become ‘prostaglandin-dependent’ in the state of hypovolaemia or with high concentrations of circulating vasoconstrictors such as norepinephrine. Central nervous system side-effects are also observed during treatments with all NSAIDS. Indomethacin [36] has been shown to reduce cerebral blood flow. The advent of Cox2 inhibitors may alter the pattern of use of NSAIDS in neurosurgery. To date, a search of the literature revealed no data on their use post craniotomy.

Incidence of chronic pain after craniotomy

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Persistent headache following craniotomy [37] (in particular base of skull surgery) has long been recognised, and several studies [40–42] have highlighted its importance. There is, however, a paucity of data regarding persistent headache after supratentorial craniotomy [43]. Headache is most often described as tension type, with episodic acute exacerbations mimicking migraine.

Harner et al. [12], interestingly, graded the scale of headache at 3 months post procedure:

  • •  
    Grade 1: a relatively minor annoyance.
  • •  
    Grade 2: headache present almost every day.
  • •  
    Grade 3: the patient requires medication every day.
  • •  
    Grade 4: the patient feels incapacitated.

Kaur et al. [43] published a study of 145 patients who underwent anterior temporal lobectomies for intractable epilepsy over a 9-year period. To eliminate confounding causes of headache, all patients studied were seizure-free, none had progressive mass lesions or persisting vascular anomalies, and none had major complications of surgery. Six per cent of patients complained of headaches that lasted for more than 2 months but less than 1 year. Twelve per cent of patients had ongoing headaches 1 year postoperatively. Of these, a quarter had medically uncontrolled headaches, whilst a third continued to require regular analgesia a year down the line from surgery. This study confirms that although the incidence of persistent head pain after supratentorial craniotomy is lower than that reported after posterior fossa procedures, the incidence is not trivial.

On the other hand, in a study of 107 patients, Gee et al. [8] found that 82% of patients had a somewhat lengthy resolution of headache following surgery. Nonetheless, all did gradually resolve and none required major medical intervention.

Harner et al. [12] reviewed 331 patients undergoing excision of acoustic neuroma and quote an incidence of postoperative headache of 23% at 3 months, 16% at 1 year and 9% at 2 years. None of their patients required additional surgical treatment. All were treated with analgesics, physiotherapy and reassurance. Schaller et al. [44] report an incidence of 34% of patients reporting severe headache and requiring medication every day. These patients still reported feeling incapacitated 3 months post surgery.

Surgical modalities to decrease the incidence of chronic pain

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Different factors [45] may play a role in preventing or reducing postoperative headache. Adherence of the cervical muscles and subcutaneous tissues to the dura, which is richly innervated, and dural tension in the case of direct dural closure, may explain postoperative headache [46]. Intradural drilling and the use of fibrin glue may be the source of aseptic meningitis contributing to the aetiology of persistent postoperative headache [47, 48]. Levo et al. [40] explored the possibility of asymmetric activation of cervicocollic reflexes being implicated in the pathogenesis of long-term headache. However, although abnormal as compared to controls, there was no significant difference in the vestibular function of postoperative patients who complained of long-term headache or were asymptomatic.

The various surgical approaches used for excision of vestibular schwannomas have been well recognised as having significantly varying results in terms of postoperative pain and morbidity. These results are important to both the surgeon and the patient during pre-operative counselling regarding the choice of surgical approach.

In the retrosigmoid approach [44] to craniotomy, headache is more prevalent in those who have the bone flap replaced (94% vs. 27%), or if there is duraplastic or direct dura closure (0% vs. 100%). Aseptic meningitis, most likely due to the use of fibrin glue and drilling of the posterior aspect of the internal auditory canal, is a major factor in the development of postoperative headache (81% vs. 2%). Schaller et al. [44] reported headache to be more prevalent in those who had the bone flap replaced (94% vs. 27%).

Koperer et al. [49] compared two groups of patients who either underwent a craniotomy or a craniectomy. Pain at 3 months as well as at 12 months was significantly less in the craniotomy group as opposed to the craniectomy group. They concluded that an osteoplastic craniotomy significantly reduces postoperative headache.

In the translabyrinthine approach [50] the incidence of headache is similar to that of the retrosigmoid approach. Again, filling of the craniotomy defect seems to decrease the incidence of long-term pain (Fig. 2).

image

Figure 2. Lateral approaches in skull base surgery. Purple, pre-auricular trans petrosal. Red, transcochlear. Blue, translabyrinthine approach. Green, presigmoid retrolabyrinthine approach.

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In the suboccipital approach [51] a small craniectomy is typically performed to get to the cerebellopontine angle. Ruckenstein et al. [13] claim that the incidence of pain within the first postoperative year is actually higher than that seen in the translabyrinthine approach despite the performance of a cranioplasty. However, by the end of the first year these differences were no longer significant.

Prevention of long-term chronic headache may therefore include the replacement of bone flap at the end of surgery [52, 53], duraplastic instead of direct dural closure, and the avoiding the use of fibrin glue or extensive drilling of the posterior aspect of the internal auditory canal.

Presentation of chronic post craniotomy headache

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

No adequate classification exists; however, some authors [54] have classified the various forms of these headaches by their resemblance to naturally occurring headache types.

Headache is the most common symptom after closed head injury, persisting for more than 2 months in 60% of patients [55, 56]. Craniotomy performed to deal with intracranial pathology secondary to trauma may lead to chronic pain as part of the syndrome of post traumatic headache.

Several symptoms usually accompany this syndrome, including cognitive, behavioural and somatic manifestations. Headaches persisting for more than 2 months are usually referred to as chronic post-traumatic headaches [57, 58]. Over time, these may take on a pattern of daily occurrence. They usually manifest as a type of chronic tension type headache or occasionally as intermittent migraine-like attacks. Rebound headaches, unfortunately, can also occur due to overuse of analgesic medications. Co-morbid psychiatric problems such as stress disorder, insomnia, depression, drug and alcohol abuse may also complicate management.

It is also worth noting that patients who have degenerative disease of the high cervical spine may experience tension type pain, so-called cervicogenic headache, because of their position during surgery [59]. This is of particular importance in patients undergoing posterior fossa surgery.

Increased pericranial muscle tension may contribute to the development of chronic tension type headache in a proportion of patients [60]. Significant headache may be produced by scar tissue surrounding the occipital nerves or by fibrous adhesions, binding neck muscles directly to the dura [46]. With movements, the neck muscles may pull the dura and cause pain.

Epilepsy secondary to craniotomy is well recognised. It would therefore not be inconceivable to suggest that a cohort of chronic pain post craniotomy may be associated with seizure-associated headaches. These headaches [61, 62] are usually migraine-like or tension headache.

A search of the literature failed to reveal any study that attempts to link chronic post craniotomy pain with an incidence of secondary epilepsy. However, it is well known that headaches associated with partial and generalised seizures are frequent and under-treated. Forderreuther et al. [63] suggest that treatment should consider both the headache syndrome and the general guidelines for treating primary headache.

Cerebrospinal fluid (CSF) leak or shunt [64] over drainage may cause orthostatic headaches. This is usually associated with diffuse pachymeningeal gadolinium enhancement, typically associated with immeasurable or very low CSF pressures. It is important to note that some patients can present with normal CSF opening pressures but still have a symptomatic CSF leak [64]. These patients usually respond to surgical treatment with complete resolution of symptoms and associated MRI abnormalities. Typical manifestations of orthostatic headaches include nausea, emesis, pain or a tight feeling of the neck, dizziness, horizontal diplopia caused by unilateral or bilateral sixth nerve palsy), photophobia, blurred vision, binasal visual field defects, and aberrations in hearing. On the other hand, some patients simply present with typical symptoms of neuropathic pain over their scar, exhibiting allodynia (pain following an innocuous stimulus) and hyperalgesia (pain disproportionate to a noxious stimulus). If treated early and aggressively, these headaches are less likely to become a permanent problem [65]. Once ‘wind-up’ occurs, the cycle is much more difficult to break [66].

Treatment of post craniotomy headache

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

The impact of recurrent chronic pain on work and social life [65] can be devastating. Further studies are required to explore the possible pathophysiological and biopsychosocial links to this prevalent problem. The surgical technique can influence the incidence of acute and chronic postoperative pain and the role of the anaesthetist is also crucial. The importance of aggressive pain relief in the acute postoperative period cannot be overemphasised.

Most of the patients who present with chronic pain can be successfully treated with various combinations of pharmacological and non-pharmacological approaches. The latter are highlighted in Table 5.

Table 5.  Non-pharmacological treatment of chronic post craniotomy headaches.
TENS
Physiotherapy
Acupuncture [70, 81]
Cognitive behaviour therapy
Adjunctive stress management techniques (relaxation)
Supportive neck collars and manual neck traction
Radio frequency nerve ablation or cryoablation

Modulation of ion channel function has been a successful area for drug development [66–68], and ion channel modulating drugs are being used to treat chronic pain. Most of the currently available ion channel-modulating drugs were developed without extensive knowledge of the molecular structure of ion channels, or an understanding of the full complexity of ion channel subtypes or knowledge of how ion channel expression is regulated during pathology. As new information on the roles that different ion channel subtypes play in pathophysiological processes becomes available, drugs will be designed to target specific subtypes via mechanisms that involve either direct channel block or modulation of ion channel functional expression.

Pharmacological treatment of chronic post craniotomy headaches

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Pharmacological treatment [69] includes the use of simple analgesics such as paracetamol with a low dose of codeine, or non-steroidal anti-inflammatory drugs. In cervicogenic type of headaches, trigger-point injections using a mixture of local anaesthetic and depomedrone may be quite effective. Capsaicin, derived from the red pepper capsicum, may be used topically when there is allodynia or hyperalgesia over the scar.

Botulinum toxin type A (Botox A) is effective in the treatment of diseases characterised by chronic pain secondary to increased muscle tone. However, two studies by Rollnik et al. [71] and Zwart et al. [72] failed to demonstrate a significant reduction in pain intensity or pressure pain thresholds.

The use of tricyclic antidepressants [73] as co-analgesics is widespread, in spite of the fact that their analgesic mode of action is complex and not fully understood. They are thought to act presynaptically, and inhibit reuptake of norepinephrine and serotonin. Additionally, they may antagonise NMDA receptors, and also have a weak mu opioid action. They are also membrane stabilisers, blocking sodium and calcium channels, as well as acting postsynaptically on α-adrenergic, cholinergic and histamine receptors. Commonly acknowledged side-effects include sedation (which may be useful when pain is associated with insomnia) and anticholinergic type of symptoms.

Several randomised controlled trials [74] have attempted to show the benefit of anticonvulsants such as carbamezepine, sodium valproate, gabapentin and Lamotrigine on neuropathic pain.

Sodium valproate [75] has a good track record particularly in the treatment of migraine-like headaches [76, 77] associated with craniotomy and post-traumatic injuries. Its pharmacological effects involve a variety of mechanisms, including increased GABAergic transmission, reduced release and/or effects of excitatory amino acids, blockade of voltage-gated sodium channels and modulation of dopaminergic and serotoninergic transmission. Sustained release formulations [78] are available that minimise fluctuations in serum drug concentrations and can be given once or twice daily. The most commonly reported adverse effects include gastrointestinal disturbances, tremor and an increase in bodyweight. Much less commonly it may be associated with platelet disorders, liver toxicity (more common if given with other anticonvulsants), pancreatitis and encephalopathy symptoms.

When the nature of pain is neuropathic, especially if associated with allodynia or hyperalgesia over the scar area, gabapentin [79, 80] may be effectively used, particularly if the patient can tolerate a pharmacologically adequate dose. Primarily marketed as an antiepileptic drug, Gabapentin has over the past decade become a mainstay in the treatment of neuropathic pain. Despite identification of GABA(B) receptors with gb1a–gb2 composition and the α2δ calcium channel subunit as putative molecular targets for gabapentin, its cellular mechanism remains elusive [81, 82]. In rat dorsal horn, gabapentin differentially regulates synaptic and extrasynaptic NMDA receptors. Gabapentin is normally given in three divided doses, initially titrated to 900 mg.day−1 over 3 days, followed by two further increases to a maximum of 2400 mg.day−1 if required by the end of week 5. The most common adverse effects include mild to moderate dizziness and somnolence. Most of these are transient and occur only during the titration phase.

Carbamezepine [70] acts by ionic conduction blockade, and is especially well known for its efficacy in the treatment of trigeminal neuralgia. Side-effects include dizziness and haematological disorders.

Lamotrigine has been reported to be effective [82] in relieving pain associated with disorders of the trigeminal nerve. It may therefore be of particular use in the treatment of chronic pain subsequent to surgery for acoustic neuroma. It is not usually used as a first line drug but may be effective in patients who have failed to respond to gabapentin, amitriptyline or sodium valproate.

Other newer anticonvulsants, e.g. topiramate and tiagabine, are under investigation.

Sodium channel blockers [83] including topical lignocaine and mexiletine may act by reducing spontaneous activity in peripheral nerves and dorsal root ganglia. Intolerable gastrointestinal side-effects can limit the use of mexiletine. Topical lidocaine gels and patches show good results, with minor side-effects, although at times it can be difficult to reliably secure patches on areas of the scalp.

Ketamine, an NMDA antagonist, can be used orally when more conventional treatment fails. Its use is limited in that it tastes foul (despite an attempt to disguise it in orange juice!) and may be associated with hallucinations and feelings of unreality.

Although the role of opioids in chronic non-malignant pain is now more accepted [84], they are often ineffective in neuropathic pain. The mu agonist oxycodone may be more effective than morphine. Tramadol also affects reuptake of the monoamines norepinephrine and serotonin. Methadone may also be useful because of its effect on NMDA receptors, although its narrow safety margin limits its use.

Sumitriptan, a 5-HT1 agonist, has been shown to be effective [40] in the treatment of persistent headache following excision of acoustic neuroma. It may also be used in patients exhibiting a migraine type of headache.

Potential future treatments

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References

Unravelling the mysteries of chronic pain may lead to better treatment options, such as drugs that act specifically on sensory neurone-specific sodium channels or as NR2B-subunit-selective N-methyl-d-aspartate receptor antagonists [77]. Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurones in the central and peripheral nervous systems. Alterations in the function of these channels appear to be intimately linked to hyperexcitability of neurones. Many types of pain appear to reflect neuronal hyperexcitability and, importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. Their contribution to the inflammatory or neuropathic pain states, the discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.

The main focus in neurosurgery and neuroanaesthesia has always been towards the preservation of neural function and cranial nerves by meticulous attention to technique on the part of the surgeon, and maintenance of as near as perfect cerebral perfusion/neuroprotection on the part of the anaesthetist [85]. As operative results have improved, we now feel that more attention should be focused on headache as one of the more significant residual symptoms whose impact of recurrent chronic pain on work and social life can be devastating.

References

  1. Top of page
  2. Summary
  3. Anatomy and innervation of the skull and its linings
  4. Surgical approaches in craniotomy
  5. Incidence of acute pain post craniotomy
  6. Pathogenesis of pain post craniotomy
  7. Role of neurotransmitters in the pathogenesis of headache
  8. Pre-emption of pain
  9. Treatment of acute pain
  10. When does acute postoperative pain become chronic pain?
  11. Incidence of chronic pain after craniotomy
  12. Surgical modalities to decrease the incidence of chronic pain
  13. Presentation of chronic post craniotomy headache
  14. Treatment of post craniotomy headache
  15. Pharmacological treatment of chronic post craniotomy headaches
  16. Potential future treatments
  17. References
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