Periprostatic nerve block (PNB) alone vs PNB combined with an anaesthetic-myorelaxant agent cream for prostate biopsy: a prospective, randomized double-arm study


Francesco Cantiello, Fatebenefratelli Hospital – Naples, Via Principe di Piemonte 28, 81050 Portico di Caserta, Italy.



To compare the efficacy of periprostatic nerve block (PNB) alone vs PNB combined with the local administration of a 1.5% lidocaine/0.3% nifedipine cream (Antrolin®, Bracco, Milan, Italy).


In a prospective, randomized, double-arm study, 200 patients were randomized to receive PNB alone (group A, 100) or PNB combined with a previous administration of the topical anaesthetic Antrolin (group B, 100). The PNB was applied by infiltrating bilaterally a solution of 5 mL lidocaine 1% and naropine 0.75%. Patients were asked to complete visual analogue scale (VAS) questionnaire (0–10) to score pain and discomfort during probe insertion (VAS1), PNB (VAS2), cores (VAS3), 30 min after biopsy (VAS4), the evening of the procedure (VAS5), and the day after biopsy (VAS6).


Pain during probe insertion in group B was significantly less than in group A (VAS1 0.82 vs 2.9; P < 0.001). Pain during periprostatic infiltration was also lower in group B than group A (VAS2 1.4 vs 3.48; P < 0.001). Pain control was similar during biopsy in the two groups (VAS3 1.28 vs 1.2; P = 0.69). The pain scored at VAS4 was significantly less in group B (0.7 vs 1.86, P < 0.001), as was VAS5 (0.68 vs 1.3, P < 0.001). There was no difference in pain perception the day after biopsy (VAS6, 0.32 vs 0.22, P = 0.14).


Antrolin placed with PNB is better than PNB alone in reducing pain and discomfort during transrectal-ultrasonography guided prostate biopsy.


prostate biopsy


periprostatic nerve block


visual analogue scale


intrarectal local anaesthesia.


Substantially many patients have moderate to severe pain during TRUS-guided prostate biopsy (PB) [1]. There is ample published evidence that anaesthesia can significantly reduce this discomfort and pain. Therefore, according to recently published guidelines, anaesthesia during TRUS-guided PB is currently considered mandatory, and PB without anaesthesia is considered ‘malpractice’[2].

It is recognized that discomfort and pain has a dual origin, arising from the introduction, persistence and movements of the TRUS probe into the anal canal and rectum, and the needle passage through the prostate capsule [3]. Among the various options, periprostatic anaesthetic infiltration of lidocaine is safe, easy to perform, highly effective and can currently be considered the ‘method of choice’[1,4–11].

Nevertheless, this anaesthetic method reduces the pain when cores are taken, but not when the transrectal probe is introduced. In our clinical experience, before introducing the transrectal probe, we apply 1.5% lidocaine/0.3% nifedipine cream (Antrolin®, Bracco, Milan, Italy). This cream is a mixture of a topical anaesthetic and a myorelaxant that acts by blocking the slow calcium channels located on the anal sphincter fibromuscular cell membranes to achieve muscle relaxation. The goal is to achieve pain control during the introduction of the transrectal probe and the subsequent lidocaine-naropine periprostatic injection.

In a prospective, randomized double-arm study we aimed to compare the efficacy of periprostatic nerve block (PNB) alone, using a mixture of 10 mL lidocaine 1% and naropine 0.75%, vs PNB combined with the previous topical administration of Antrolin cream in the palliation of pain caused by TRUS PB.


In all, 200 patients presenting with abnormal DRE findings, or an increased PSA level with or without abnormal DRE findings, or lesions suspicious for malignancy on TRUS with or without an abnormal DRE, were considered for study inclusion. Patients taking anticoagulants or reporting anal or rectal pathology, allergy to lidocaine, naropine or calcium antagonists, a history of bleeding tendency or of TRUS-guided PB, were excluded. Informed consent was obtained from all participants.

Patients were randomized to receive PNB alone (a mixture of 5 mL lidocaine 1% and naropine 0.75%) injected into either neural bundles (group A, 100), or PNB combined with previous Antrolin (group B, 100).

As antibiotic prophylaxis patients were given oral levofloxacin 500 mg daily starting the evening before the sampling until 4 days after biopsy. A cleaning enema was administered the evening before and the morning of the biopsy. TRUS-guided PBs were taken with the patient in the lithotomy position, using an ultrasound scanner with a 7.5 MHz endorectal multiplanar ‘end-fire’ probe. The probe was rectilinear with a basal and middle diameter of 16 mm and apical diameter (corresponding transducer) of 18 mm. Before biopsy the prostate volume was measured using the ellipsoid formula, the most common method of determining prostate volume.

In both group A and B patients the mixture of 5 mL lidocaine 1%+ naropine 0.75% was injected bilaterally into the neurovascular bundles at the seminal vesicle-bladder-rectum angle on either side with a 22 G spinal needle during TRUS. In the group B patients only, 10 mL of Antrolin cream was applied around the anal ring, in the anus and rectum 10 min before introducing the TRUS probe.

After 5 min PBs were taken using an 18 G Tru-Cut needle powered by a biopsy gun. In all patients, 12 systematic prostatic cores, including six parasagittal and six lateral, were taken, covering the base, mid zones and apex. Additional cores were obtained from areas of suspected malignancy.

All patients were hospitalized in a ‘One-Day’ surgery centre and observed for ≥2 h after the procedure. They were discharged home only if they had voided successfully. During their hospital stay patients were asked to complete a questionnaire that included a visual analogue scale (VAS) of 0–10 cm to score the pain/discomfort experienced: (i) during the introduction and presence of the probe in the rectum (VAS1); (ii) during the PNB block (VAS2); (iii) during the biopsy procedure (VAS3); (iv) 30 min after the procedure (VAS4); (v) the evening of the same day (VAS5); and (vi) the day after procedure (VAS6). Also, patients were asked to report any complications and side-effects.

Topical anaesthesia, PNB and biopsy were administered by the same operator (F.C.). After the procedure, another operator (V.I.) asked the patients to complete the VAS questionnaires. The blood pressure and heart rate were measured before and after the procedure.

Data were analysed using a one-way anova, assessing the quantitative dependent variable against an (independent) variable, to assess differences among the means, with P < 0.05 considered to indicate statistical significance.


The two groups were similar for cancer rate, age, serum PSA level and total prostate volume (Table 1). The perception of pain during probe insertion in group B (VAS1) was significantly less than in group A (Table 1), as was the pain during PNB (VAS2). However, pain control was similar during biopsy in the two groups (VAS3). The pain 30 min after biopsy was significantly less in group B (VAS4), as was the pain recorded in the evening (VAS5). There was no difference in pain perception the day after biopsy (VAS6; Table 1).

Table 1.  The percentage of cancer, age, PSA value, total prostate volume in groups A and B
VariableMean (sd) or nP
Group AGroup B
N total /n with cancer100/40100/37>0.05
Age, years 67.4 (4.1) 62 (5.6)>0.05
PSA, ng/mL  11.6 (4.7) 12.7 (3.4)>0.05
Total prostate volume, mL 54.9 (13.3) 61.1 (14.5)>0.05
VAS scores
VAS1 (probe insertion)  2.9 (1.61)  0.82 (0.95)<0.001
VAS 2 (PNB)  3.48 (1.32)  1.40 (0.89)<0.001
VAS 3 (biopsy)  1.28 (1.77)  1.20 (0.98)  0.690
VAS 4 (after 30 min)  1.86 (1.64)  0.70 (0.73)<0.001
VAS 5 (evening)  1.30 (0.84)  0.68 (0.79)<0.001
VAS 6 (next day)  0.32 (0.54)  0.22 (0.41)  0.140
Minor complications, n
Persistent haematuria  7  8 
Mild rectal bleeding 12 16 
Acute urinary retention  1  1 
Fever, 38 °C  1  2 
Dysuria 10  11 
Haematospermia 23 20 

There were no general or local side-effects associated with local anaesthesia, and no change in cardiovascular variables (blood pressure and heart rate) associated with the possible systemic absorption of nifedipine. No major complications, including sepsis or severe rectal bleeding, were reported in any patient. The minor complications are also listed in Table 1; there was no statistically significant difference between the groups.


PB is associated with significant pain and discomfort to the patient. Crundwell et al.[12] reported moderate to severe pain in a quarter of their patients during TRUS-guided PB. Irani et al.[13] found that 16% of their patients reported meaningful pain during biopsy, recorded as a VAS score of >5, and that 19% would refuse to undergo further TRUS and PB with no analgesia.

The discomfort during the procedure does not appear to be proportional to the number of cores taken. In a prospective randomized study comparing a 12- with a six-core biopsy protocol, Naughton et al.[14] reported no statistically significant difference in the two procedures for any mean pain level, neither at biopsy nor subsequently. Chang et al.[15] noted no correlation between the number of biopsies taken and pain score, but they found that age significantly affected the pain score, with younger patients experiencing more pain than older ones.

Given that the biopsy needle pierces the rectal wall above the dentate line in an area of decreased sensitivity, most pain during PB is associated with the needle penetrating the prostatic capsule, which is richly innervated with autonomic fibres, the latter conveying visceral sensation to the spinal cord. The innervation of the prostate is derived from the caudal roots of S2 to S5 and from the sympathetic chain via the presacral and hypogastric neural plexus. These fibres ramify in the prostatic plexus and subsequently travel with the prostatic vascular pedicles, which are located at the posterolateral aspect of the prostatic base [4,16].

Based on this considerations, Nash et al.[4] described, for the first time in a study published in 1996, the PNB block before PB, using a unilateral injection of 5 mL 1% lidocaine into the region of the prostatic vascular pedicle at the base of the prostate, just lateral to the junction between the prostate and seminal vesicle.

Currently there is ample published evidence that PNB is a safe procedure, easy to perform and effectively decreases patient pain and discomfort [5–11,17]. However, PNB does not completely eliminate the pain. Indeed, PNB cannot reduce pain associated with the introduction, persistence and movements of the TRUS probe into the anal canal and rectum, that might be even more painful than the biopsy [3]. Therefore, intrarectal local anaesthesia (IRLA) is required to decrease the pain associated with the TRUS probe in the first part of the biopsy procedure. Recently, a meta-analysis involving 466 patients and comparing IRLA with placebo showed that IRLA was associated with pain reduction during the biopsy procedure [18].

However, in several randomized studies [6,19–22], IRLA alone appears to be inferior to PNB in term of analgesic efficacy. Thus it is intuitive that the ‘optimum’ could be an additional IRLA before PNB. This approach was first described by Obek et al.[23], who showed that the combination of PNB and intrarectal instillation of lidocaine was better than PNB alone or i.v. tramadol, and concluded that this combined local anaesthesia could be accepted as ‘the new standard’. Nevertheless, they evaluated pain from the procedure as a whole and not as pain specifically from any one step of the biopsy procedure.

Also Raber et al.[24] showed that PNB combined with preliminary perianal and intrarectal administration of lidocaine-prilocaine cream, compared with PNB alone, significantly reduced PB related-pain, by reducing discomfort during the introduction of the TRUS probe and periprostatic infiltration. Pain of only the sampling part was not reduced. They showed that this form of combined anaesthesia might be of maximum benefit for younger patients. Yun et al.[25] reported that additional instillation of lidocaine gel before PNB for pain relief during TRUS-guided PB provides effective analgesia. By contrast, they showed that the analgesic effect is greatest and statistically significant while taking the biopsy cores, whereas during PNB and 20 min after PB patients who received lidocaine gel instillation had less pain than patients who did not, but there was no statistically significant difference. The authors did not measure the pain associated with TRUS probe insertion.

In the present study, the IRLA significantly reduced PB-related pain by reducing discomfort during the introduction of the TRUS probe in the first part of the biopsy procedure. Furthermore, IRLA also attenuated the pain reported 30 min after the biopsy and the evening of the same day, thus enhancing the ‘mid-term’ analgesic effect. The peculiarity of our study is the use of Antrolin cream, a mixture of a topical short-acting anaesthetic and a myorelaxant agent, designed to provide a 12-h palliation of symptoms from anal fissures. This leads to better pain control during the TRUS probe introduction, as a result of both the anaesthetic and the myorelaxant effect, and to a longer lasting palliation of the discomfort due to the pharmacokinetics of the drug and its duration of action.

The use of a myorelaxant cream was initially proposed by Rochester et al.[26]. In a double-blind randomized controlled trial they showed a statistically significant decrease in the level of pain experienced during TRUS-guided PB after the administration of topical 0.2% glyceryl trinitrate paste vs placebo. Subsequently, McCabe et al.[27] showed that PNB combined with administration of 0.2% glyceryl trinitrate paste vs PNB or placebo significantly reduced the discomfort associated with TRUS-guided PB, in particular during insertion of the probe.

We used a 10-mL mixture of lidocaine 1%/naropine 0.75% (short- and long-acting anaesthetics) for the PNB, avoiding a rebound pain effect, the latter with lidocaine alone being addressed by Lee-Elliot et al.[28]. In a randomized trial comparing lidocaine vs lidocaine and a long-acting anaesthetic periprostatic injection, they found that the combination significantly attenuated the 1-h rebound pain seen after short-acting anaesthesia alone. Improved pain scores were also reported during the subsequent week.

Our combined local anaesthesia method is a safe and easy procedure, and should be used in all patients, especially if potentially candidates for re-biopsy. There were no general or local side-effects associated with local anaesthesia, and no changes in the cardiovascular variables.

We did not use a control placebo group with periprostatic injection of saline solution, because we consider it to be unethical. Future research should be focused on the effect of TRUS probe geometry, size and method of introduction on the anal component of pain.

In conclusion, we showed the superiority of the additional topical application of lidocaine-nifedipine cream in the anal canal and rectum combined with PNB (using a mixture of short- and long-acting anaesthetic) vs PNB alone. The intrarectal local anaesthesia produced an additional analgesic effect when the TRUS probe was inserted and PNB applied, and at 30 min to a few hours after PB. The method is safe and rapid, and should be considered in all patients having TRUS-guided PB.


None declared.