• 1
    Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988; 12: 12337.
  • 2
    Maier SF, Watkins LR. Cytokines for psychologists: implications of bi-directional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Rev 1998; 105: 83107.
  • 3
    Kent S, Bluthe RM, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci 1992; 13: 2428.
  • 4
    Watkins LR, Maier SF, Goehler LE. Minireview: cytokine-to-brain communication: a review & analysis of alternative mechanisms. Life Sci 1995; 57: 101126.
  • 5
    Watkins LR, Maier SF. The pain of being sick: implications of immune-to-brain commuication for understanding pain. Annu Rev Psychol 2000; 51: 2957.
  • 6
    Ader R. On the development of psychoneuroimmunology. Eur J Pharmacol 2000; 405: 16776.
  • 7
    Dinarello CA. Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 1997; 11: 91103.
  • 8
    Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 2000; 23: 61825.
  • 9
    Rothwell NJ, Luheshi G, Toulmond S. Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology. Pharmacol Ther 1996; 69: 8595.
  • 10
    Ignatowski TA, Noble BK, Wright JR, Gorfien JL, Heffner RR, Spengler RN. Neuronal-associated tumor necrosis factor (TNFa): its role in noradrenergic functioning and modification of its expression following antidepressant drug administration. J Neuroimmunol 1997; 79: 8490.
  • 11
    Parnet P, Kelley KW, Bluthe RM, Dantzer R. Expression and regulation of interleukin-1 receptors in the brain. Role in cytokines-induced sickness behavior. J Neuroimmunol 2002; 125: 514.
  • 12
    Tazi A, Dantzer R, Crestani F, Le Moal M. Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity. Brain Res 1988; 473: 36971.
  • 13
    Maier SF, Wiertelak EP, Martin D, Watkins LR. Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin. Brain Res 1993; 623: 3214.
  • 14
    Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 2001; 933: 22234.
  • 15
    Banks WA, Kastin AJ, Broadwell RD. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation 1995; 2: 2418.
  • 16
    Quan N, Herkenham M. Connecting cytokines and brain: a review of current issues. Histol Histopathol 2002; 17: 27388.
  • 17
    Romeo HE, Tio DL, Rahman SU, Chiappelli F, Taylor AN. The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 2001; 115: 91100.
  • 18
    Goehler LE, Gaykema RPA, Hansen MK, Andreson K, Maier SF, Watkins LR. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 2000; 85: 4959.
  • 19
    Hansen MK, O'Connor KA, Goehler LE, Watkins LR, Maier SF. The contribution of the vagus nerve in interleukin-1beta-induced fever is dependent on dose. Am J Physiol 2001; 280: R92934.
  • 20
    Azab AN, Kaplanski J. Vagotomy attenuates the effect of lipopolysaccharide on body temperature of rats in a dose-dependent manner. J Endotoxin Res 2001; 7: 35964.
  • 21
    Ek M, Kurosawa M, Lundeberg T, Ericsson A. Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins. J Neurosci 1998; 18: 94719.
  • 22
    Goehler LE, Gaykema R, Nguyen K, Hansen M, Maier SF, Watkins LR. Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems? J Neurosci 1999; 19: 2799806.
  • 23
    Maier SF, Wiertelak EP, Watkins LR. Endogenous pain facilitatory systems: anti-analgesia and hyperalgesia. Am Pain Soc J 1992; 1: 1918.
  • 24
    Wiertelak EP, Smith KP, Furness L et al. Acute and conditioned hyperalgesic responses to illness. Pain 1994; 56: 22734.
  • 25
    Wiertelak EP, Roemer B, Maier SF, Watkins LR. Comparison of the effects of nucleus tractus solitarius and ventral medulla lesions on illness-induced and subcutaneous formalin-induced hyperalgesias. Brain Res 1997; 748: 14350.
  • 26
    Watkins LR, Wiertelak EP, Goehler L et al. Neurocircuitry of illness-induced hyperalgesia. Brain Res 1994; 639: 28399.
  • 27
    Watkins LR, Wiertelak EP, Goehler LE, Smith KP, Martin D, Maier SF. Characterization of cytokine-induced hyperalgesia. Brain Res 1994; 654: 1526.
  • 28
    Watkins LR, Goehler LE, Relton J, Brewer MT, Maier SF. Mechanisms of tumor necrosis factor-a (TNF-a) hyperalgesia. Brain Res 1995; 692: 24450.
  • 29
    Watkins LR, Deak T, Silbert L et al. Evidence for involvement of spinal cord glia in diverse models of hyperalgesia. Proc Soc Neurosci 1995; 21: 897.
  • 30
    Watkins LR, Milligan ED, Maier SF. Immune and glial involvement in physiological and pathological exaggerated pain states. In: DostrovskyJO, CarrDB, KoltzenbergM, eds. Advances in Pain Research and Therapy. Seattle, WA: IASP Press, 2003; 36985.
  • 31
    Wiertelak EP, Furness LE, Watkins LR, Maier SF. Illness-induced hyperalgesia is mediated by a spinal NMDA-nitric oxide cascade. Brain Res 1994; 664: 916.
  • 32
    Watkins LR, Wiertelak EP, Furness LE, Maier SF. Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids. Brain Res 1994; 664: 1724.
  • 33
    Bennett GJ. Neuropathic pain. In: WallPD, MelzackR, eds. Textbook of Pain. New York: Churchill Livingston, 1994; 20124.
  • 34
    Foley KM. Opioids and chronic neuropathic pain. N Engl J Med 2003; 348: 127981.
  • 35
    Clatworthy AL. Evolutionary perspectives of cytokines in pain. In: WatkinsLR, MaierSF, eds. Cytokines and Pain. Basel: Birkhauser, 1999; 2138.
  • 36
    Clatworthy AL, Grose E. Immune-mediated alterations in nociceptive sensory function in Aplysia californica. J Exp Biol 1999; 202: 62330.
  • 37
    Watkins LR, Maier SF. Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 2002; 82: 9811011.
  • 38
    Myers RR, Wagner R, Sorkin LS. Hyperalgesic actions of cytokines on peripheral nerves. In: WatkinsLR, MaierSF, eds. Cytokines and Pain. Basel: Birkause, 1999; 13358.
  • 39
    Myers RR, Heckman HM, Rodriguez M. Reduced hyperalgesia in nerve-injured WLD mice: relationship to nerve fiber phagocytosis, axonal degeneration and regeneration in normal mice. Exp Neurol 1996; 141: 94101.
  • 40
    Clatworthy AL, Illich PA, Castro GA, Walters ET. Role of periaxonal inflammation in the development of thermal hyperalgesia and guarding behavior in a rat model of neuropathic pain. Neurosci Lett 1995; 184: 58.
  • 41
    Kleinschnitz C, Brinkhoof J, Zelenka M, Sommer C, Stoll G. The extent of cytokine induction in peripheral nerve lesions depends on the mode of injury and NMDA reeptor signaling. J Neuroimmunol 2004; 149: 7783.
  • 42
    Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 2004; 361: 1847.
  • 43
    Sommer C, Petrausch S, Lindenlaub T, Toyka KV. Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci Lett 1999; 270: 258.
  • 44
    Lindenlaub T, Teuteberg P, Hartung T, Sommer C. Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res 2000; 866: 1522.
  • 45
    Twining CM, Sloane EM, Milligan ED et al. Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats. Pain 2004; 110: 299309.
  • 46
    Scafers M, Brinkhoof J, Neukirchen S, Marziniak M, Sommer C. Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice. Neurosci Lett 2001; 310: 1136.
  • 47
    Liu T, VanRooijen N, Tracey DJ. Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain 2000; 86: 2532.
  • 48
    Cui JG, Holmin S, Mathiesen T, Meyerson BA, Linderoth B. Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy. Pain 2000; 88: 23948.
  • 49
    Lindenlaub T, Sommer C. Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol 2003; 105: 593602.
  • 50
    Maves TJ, Pechman PS, Gebhart GF, Meller ST. Possible chemical contribution from chromic gut sutures produces disorders of pain sensation like those seen in man. Pain 1993; 54: 5769.
  • 51
    Eliav E, Herzberg U, Ruda MA, Bennett GJ. Neuropathic pain from an experimental neuritis of the rat sciatic nerve. Pain 1999; 83: 16982.
  • 52
    Chacur M, Milligan ED, Gazda L et al. A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain 2001; 94: 23144.
  • 53
    Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumor necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibers. Neuroscience 1997; 81: 25562.
  • 54
    Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 1996; 7: 2897901.
  • 55
    Sorkin LS, Doom CM. Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat. JPNS 2000; 5: 12.
  • 56
    Chacur M, Milligan ED, Sloan EM et al. Snake venom phospholipase A2s (Asp49 and Lys49) induce mechanical allodynia upon peri-sciatic administration: involvement of spinal cord glia, proinflammatory cytokines and nitric oxide. Pain 2004; 108: 18091.
  • 57
    Ma W, Eisenach JC. Cyclooxygenase 2 in infiltrating inflammatory cells in injured nerve is universally up-regulated following various types of peripheral nerve injury. Neuroscience 2003; 121: 691704.
  • 58
    Takahashi M, Kawaguchi M, Shimada K, Konishsi N, Furuya H, Nakashima T. Cyclooxygenase-2 expression in Schwann cells and macrophages in the sciatic nerve after single spinal nerve injury in rats. Neurosci Lett 2004; 363: 2036.
  • 59
    Schafers M, Marziniak M, Sorkin LS, Yaksh TL, Sommer C. Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat. Exp Neurol 2004; 185: 1608.
  • 60
    Liu T, Knight KR, Tracey DJ. Hyperalgesia due to nerve injury-role of peroxynitrite. Neuroscience 2000; 97: 12531.
  • 61
    Zuo Y, Perkins NM, Tracey DJ, Geczy CL. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 2003; 105: 46779.
  • 62
    Perkins NM, Tracey DJ. Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 2000; 101: 74557.
  • 63
    Pollock J, McFarlane SM, Connell MC et al. TNF-alpha receptors simultaneously activate Ca2+ mobilisation and stress kinases in cultured sensory neurones. Neuropharmacology 2002; 42: 93106.
  • 64
    Irnich D, Tracey DJ, Polten J, Burgstahler R, Grafe P. ATP stimulates peripheral axons in human, rat and mouse – differential involvement of A(2B) adenosine and P2X purinergic receptors. Neuroscience 2002; 2002: 1239.
  • 65
    Lang PM, Sippel W, Schmidbauer S, Irnich D, Grafe P. Functional evidence for P2X receptors in isolated human vagus nerve. Anesthesiology 2003; 99: 2325.
  • 66
    Carlton SM, Hargett GL, Coggeshall RE. Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat. Neuroscience 2001; 105: 95769.
  • 67
    Bernardini N, Neuhuber W, Reeh PW, Sauer SK. Morphological evidence for functional capsaicin receptor expression and calcitonin gene-related peptide exocytosis in isolated peripheral nerve axons of the mouse. Neuroscience 2004; 126: 58590.
  • 68
    Hanani M, Huang TY, Cherkas PS, Ledda M, Pannese E. Glial cell plasiticity in sensory ganglia induced by nerve damage. Neuroscience 2002; 114: 27983.
  • 69
    Kagan BL, Baldwin RL, Munoz D, Wisnieski BJ. Formation of ion-permeable channels by tumor necrosis factor-alpha. Science 1992; 255: 142730.
  • 70
    Wilkinson MF, Earle ML, Triggle CR, Barnes S. Interleukin-1 beta, tumor necrosis factor-alpha, and LPS enhance calcium channel current in isolated vascular smooth cells of rat tail artery. FASEB J 1996; 10: 78591.
  • 71
    Qiu Z, Sweeney DD, Netzeband JG, Gruol DL. Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci 1998; 18: 1044556.
  • 72
    Weick M, Cherkas PS, Hartig W, Pannicke T, Uckermann O, Bringmann A, Tal M, Reichenbach A, Hanani M. P2 receptors in satellite glial cells in trigeminal ganglia of mice. Neuroscience 2003; 2003: 96977.
  • 73
    Morris R, Southam E, Braid DJ, Garthwaite J. Nitric oxide may act as a messenger between dorsal root ganglion neurones and their satellite cells. Neurosci Lett 1992; 137: 2932.
  • 74
    Woodham P, Anderson PN, Nadim W, Turmaine M. Satellite cells surrounding axotomised rat dorsal root ganglion cells increase expression of a GFAP-like protein. Neurosci Lett 1989; 98: 812.
  • 75
    Ramer MS, Kawaja MD, Henderson JT, Roder JC, Bisby MA. Glial overexpression of NGF enhances neuropathic pain and adrenergic sprouting into DRG following chronic sciatic constriction in mice. Neurosci Lett 1998; 251: 536.
  • 76
    Zhou XF, Deng YS, Chie ET et al. Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat. Eur J Neurosci 1999; 11: 171122.
  • 77
    Pannese E, Ledda M, Huang TY, Cherkas PS, Hanani M. Satellite cell reactions to axon injury of sensory ganglion neurons: increase in number of gap junctions and formation of bridges connectings previously separate perineuronal sheaths. Anat Embryol 2003; 206: 33747.
  • 78
    Hu P, McLachlan EM. Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 2002; 112: 2338.
  • 79
    McKay SM, McLachlan EM. Inflammation of rat dorsal root ganglia below a mid-thoracic spinal transection. Neuroreport 2004; 15: 17836.
  • 80
    Schafers M, Sorkin LS, Geis C, Shubayev VI. Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat. Neurosci Lett 2003; 347: 17982.
  • 81
    Ohtori S, Takahashi K, Moriya H, Myers RR. TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine 2004; 29: 10828.
  • 82
    Shubayev V, Myers RR. Axonal transport of TNFa in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 2001; 114: 4856.
  • 83
    Schafers M, Lee DH, Brors D, Yaksh TL, Sorkin LS. Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci 2003; 23: 302838.
  • 84
    Chung K, Lee BH, Yoon YW, Chung JM. Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model. J Comp Neurol 1996; 376: 24152.
  • 85
    Morioka N, Inoue A, Hanada T et al. Nitric oxide synergistically potentiates interleukin-1 beta induced increase of cyclooxygenase-2 mRNA levels, resulting in the facilitation of substance P release from primary afferent neurons: involvement of cGMP-independent mechanisms. Neuropharmacology 2002; 43: 86876.
  • 86
    Morioka N, Takeda K, Kumagai K et al. Interleukin-1beta-induced substance P release from rat cultured primary afferent neurons driven by two phospholipase A2 enzymes: secretory type IIA and cytosolic type IV. J Neurochem 2002; 80: 98997.
  • 87
    Hou L, Li W, Wang X. Mechanism of interleukin-1beta-induced calcitonin gene-related peptide production from dorsal root ganglion neurons of neonatal rats. J Neurosci Res 2003; 73: 18897.
  • 88
    Kang JD, Georgescu HI, McIntyre-Larkin L et al. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1996; 21: 2717.
  • 89
    Olmarker K, Rydevik B. Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica. Spine 2001; 26: 8639.
  • 90
    Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine 1996; 21: 21824.
  • 91
    Kawakami M, Matsumoto T, Kuribayashi K, Tamaki T. mRNA expression of interleukins, phospholipase A2, and nitric oxide synthase in the nerve root and dorsal root ganglion induced by autologous nucleus pulposus in the rat. J Orthop Res 1999; 17: 9416.
  • 92
    Kawakami M, Tamaki T, Matsumoto T, Kuribayashi K, Takenaka T, Shinozaki M. Role of leukocytes in radicular pain secondary to herniated nucleus pulposus. Clin Orthop 2000; 376: 26877.
  • 93
    Solovieva S, Kouhia S, Leino-Arjas P, Ala-Kokko L, Luoma K, Raininko R, Saarela J, Riihimaki H. Interleukin 1 polymophisms and intervertebral disc degeneration. Epidemiology 2004; 15: 62633.
  • 94
    Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H. Possible association of interleukin 1 gene locus polymoprhisms with low back pain. Pain 2004; 109: 819.
  • 95
    Igarashi T, Kikuchi S, Shubayev V, Myers RR. Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular histologic, and behavioral comparisons in rats. Spine 2000; 25: 297580.
  • 96
    Kawakami M, Hashizume H, Nishi H, Matsumoto T, Tamaki T, Kuribayashi K. Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat. J Orthop Res 2003; 21: 9416.
  • 97
    Anzai H, Hamba M, Onda A, Konno S, Kikuchi S. Epidural application of nucleus pulposus enhances nociresponses of rat dorsal horn neurons. Spine 2002; 27: E505.
  • 98
    Onda A, Yabuki S, Kikuchi S. Effects of neutralizing antibodies to tumor necrosis factor-alpha on nucleus pulposus-induced abnormal nociresponses in rat dorsal horn neurons. Spine 2003; 28: 96772.
  • 99
    Cuellar JM, Montesano PX, Carstens E. Role of TNF-alpha in sensitization of nociceptive dorsal horn neurons induced by application of nucleus pulposus to L5 dorsal root ganglion in rats. Pain 2004; 110: 57887.
  • 100
    Onda A, Hamba M, Yabuki S, Kikuchi S. Exogenous tumor necrosis factor-alpha induces abnormal discharges in rat dorsal horn neurons. Spine 2002; 27: 161824.
  • 101
    Aoki Y, Rydevik B, Kikuchi S, Olmarker K. Local application of disc-related cytokine on spinal nerve roots. Spine 2002; 27: 16147.
  • 102
    Kawakami M, Tamaki T, Hashizume H, Weinstein JN, Meller ST. The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat. Spine 1997; 22: 10749.
  • 103
    Arruda JL, Colburn RW, Rickman AJ, Rutkowski MD, DeLeo JA. Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. Brain Res Mol Brain Res 1998; 62: 22835.
  • 104
    Sweitzer SM, Colburn RW, Rutkowski M, DeLeo JA. Acute peripheral inflammation induces moderate glial activation and spinal IL-1 beta expression that correlates with pain behavior in the rat. Brain Res 1999; 829: 20921.
  • 105
    Watkins LR, Maier SF. Glia: a novel drug discovery target for clinical pain. Nat Rev Drug Discov 2003; 2: 97385.
  • 106
    Milligan ED, Twining C, Chacur M et al. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain. J Neurosci 2003; 23: 102640.
  • 107
    Milligan ED, O'Connor KA, Nguyen KT et al. Intrathecal HIV-1 envelope glycoprotein gp120 induces enhance pain states mediated by spinal proinflammatory cytokines. J Neurosci 2001; 21: 280819.
  • 108
    Sweitzer SM, Martin D, DeLeo JA. Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 2001; 103: 52939.
  • 109
    Sjostrand J. Neuroglial proliferation in the hypoglossal nucleus after nerve injury. Exp Neurol 1971; 30: 17889.
  • 110
    Garrison CJ, Dougherty PM, Carlton SM. GFAP expression in lumbar spinal cord of naive and neuropathic rats treated with MK-801. Exp Neurol 1994; 129: 23743.
  • 111
    Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 1991; 565: 17.
  • 112
    DeLeo JA, Colburn RW. Proinflammatory cytokines and glial cells: their role in neuropathic pain. In: WatkinsL, ed. Cytokines and Pain. Basel: Birkhauser, 1999; 15982.
  • 113
    Chacur M, Gutierrez JM, Milligan ED et al. Snake venom components enhance pain upon subcutaneous injection: an initial examination of spinal cord mediators. Pain 2004; 111: 6576.
  • 114
    Watkins LR, Martin D, Ulrich P, Tracey KJ, Maier SF. Evidence for the involvement of spinal cord glia in subcutaneous formalin induced hyperalgesia in the rat. Pain 1997; 71: 22535.
  • 115
    Meller ST, Dyskstra C, Grzybycki D, Murphy S, Gebhart GF. The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharmacology 1994; 33: 14718.
  • 116
    Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 2003; 306: 62430.
  • 117
    Ledeboer A, Sloane E, Chacur M, Milligan ED, Maier SF, Watkins LR. Selective inhibition of spinal cord microglial activation attenuates mechanical allodynia in rat models of pathological pain. Proc Soc Neurosci 2003; 29: 345.
  • 118
    Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci 2001; 24: 4505.
  • 119
    Reeve AJ, Patel S, Fox A, Walker K, Urban L. Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur J Pain 2000; 4: 24757.
  • 120
    Constandil L, Pelissier T, Soto-Moyano R et al. Interleukin-1beta increases spinal cord wind-up activity in normal but not in monoarthritic rats. Neurosci Lett 2003; 342: 13942.
  • 121
    Viviani B, Bartesaghi S, Goardoni F et al. Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 2003; 23: 8692700.
  • 122
    Moriguchi S, Mizoguchi Y, Tomimatsu Y et al. Potentiation of NMDA receptor-mediated synpatic responses by microglia. Mol Brain Res 2003; 119: 1609.
  • 123
    Bezzi P, Gundersen V, Galbete JL et al. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 2004; 7: 61320.
  • 124
    Benz B, Grima G, Do KQ. Glutamate-induced homocysteic acid release from astrocytes: possible implication in glia-neuron signaling. Neuroscience 2004; 124: 37786.
  • 125
    Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci 2003; 23: 2899910.
  • 126
    Beaujouan JC, Daguet Montety de MC, Torrens Y, Saffroy M, Dietl M, Glowinski J. Marked regional heterogeneity of 125I-Bolton Hunter substance P binding and substance P-induced activation of phospholipase C in astrocyte cultures from the embryonic or newborn rat. J Neurochem 1990; 54: 66975.
  • 127
    Marriott D, Wilkin GP, Coote PR, Wood JN. Eicosanoid synthesis by spinal cord astrocytes is evoked by substance P; possible implications for nociception and pain. Adv Prostaglandin Thromboxane Leukot Res 1991; 21B: 73941.
  • 128
    Aicher SA, Sharma S, Cheng PY, Pickel VM. The N-methyl-D-aspartate (NMDA) receptor is postsynaptic to substance P-containing axon terminals in the rat superficial dorsal horn. Brain Res 1997; 772: 7181.
  • 129
    Tsuda M, Shigemoto-Mogami Y, Koizumi S et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003; 424: 77883.
  • 130
    Inoue K. Microglial activation by purines and pyrimidines. Glia 2002; 40: 15663.
  • 131
    Shigemoto-Mogami Y, Koizumi S, Tsuda M, Ohsawa K, Kohsaka S, Inoue K. Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5. J Neurochem 2001; 78: 133949.
  • 132
    Hide I, Tanaka M, Inoue A et al. Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia. J Neurochem 2000; 2000: 96572.
  • 133
    Inoue K, Koizumi S, Tsuda M, Shigemoto-Mogami Y. Signaling of ATP receptors in glia-neuron interaction and pain. Life Sci 2003; 74: 18997.
  • 134
    Wu Y, Willcockson HH, Maixner W, Light AR. Suramin inhibits spinal cord microglia activation and long-term hyperalgesia induced by formalin injection. J Pain 2004; 5: 4855.
  • 135
    Holguin, A., O'Connor KA, Biedenkapp J et al. HIV-1 gp120 stimulates proinflammatory cytokine-mediated pain facilitation via activation of nitric oxide synthase-I (nNOS). Pain 2004; 110: 51730.
  • 136
    Verge GM, Milligan ED, Maier SF, Watkins LR, Naeve GS, Foster AC. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal versus neuropathic pain conditions. Eur J Neurosci 2004; 20: 115060.
  • 137
    Milligan ED, Zapata V, Chacur M et al. Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation. Eur J Neurosci 2004; 20: 2294302.
  • 138
    Chapman G, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJLM. Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 2000; 20 RC87: 15.
  • 139
    Vabulas RM, Ahmad-Nejad P, DaCosta C et al. Endocytosed HSP60s use Toll-like receptor 2 (TLR2) and TLR4 to activate the Toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 2001; 276: 313329.
  • 140
    Bhat NR, Sharma KK. Microglial activation by the small heat shock protein, alpha-crystallin. Neuroreport 1999; 10: 286973.
  • 141
    Costigan M, Mannion RJ, Kendall G et al. Heat shock protein 27: developmental regulation and expression after peripheral nerve injury. J Neurosci 1998; 18: 5891900.
  • 142
    Wieseler-Frank J, Kwiecien O, Jekich B, Maier SF, Watkins LR. Putative neuron-to-glia signals synergize to enhance interleukin-1 production by rat dorsal spinal cord glial cells in vitro. Proc Soc Neurosci 2004; 34: 518.
  • 143
    Tanga FY, Raghavendra V, DeLeo JA. Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int 2004; 45: 397407.
  • 144
    Raghavendra V, Tanga FY, DeLeo JA. Complete Freund's adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 2004; 20: 46773.
  • 145
    Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 3128.
  • 146
    Araque A, Parpura, V., Sanzgiri, R.P., Haydon, P.G. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 1999; 22: 20815.
  • 147
    Perea G, Araque A. Communication between astrocytes and neurons: a complex language. J Physiol 2002; 96: 199207.
  • 148
    McQuay H, Carroll D, Jadad AR, Wiffen P, Moore A. Anticonvulsant drugs for management of pain: a systematic review. Br Med J 1995; 311: 104752.
  • 149
    McQuay HJ, Tramer M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68: 21727.