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Spinal and Peripheral GABA-A and B Receptor Agonists for the Alleviation of Mechanical Hypersensitivity following Compressive Nerve Injury in the Rat  

Jeon, Young Hoon (Departments physiology and Yonsei University College of Medicine)
Yoon, Duck Mi (Departments Anesthesiology & Pain Medicine Yonsei University College of Medicine)
Nam, Taick Sang (Departments physiology and Yonsei University College of Medicine)
Leem, Joong Woo (Departments physiology and Yonsei University College of Medicine)
Paik, Gwang Se (Departments physiology and Yonsei University College of Medicine)
Publication Information
The Korean Journal of Pain / v.19, no.1, 2006 , pp. 22-32 More about this Journal
Abstract
Background: This study was conducted to investigate the roles of the spinal and peripheral ${\gamma}$-aminobutyric acid (GABA)- ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). Methods: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. Results: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. Conclusions: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.
Keywords
back pain; compression of dorsal root ganglion; compressive neuropathy; GABA receptor; mechanical hyperalgesia;
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1 Andersson GB: Epidemiological features of chronic low-back pain. Lancet 1999; 354: 581-5   DOI   ScienceOn
2 Seltzer Z, Dibner R, Shir Y: A novel behavioral model of neuropathic pain pain disorders produced in rats by partial sciatic nerve injury. Pain 1990; 43: 205-18
3 Hu SJ, Xing JL: An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 1998; 77: 15-23   DOI   ScienceOn
4 Woolf CJ: Dissecting out mechanisms responsible for peripheral neuropathic pain: Implications for diagnosis and therapy. Life Sci 2004; 74: 2605-10   DOI   ScienceOn
5 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Meth 1994; 53: 55-63   DOI   ScienceOn
6 Malan TP, Mata HP, Porreca F: Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology 2002; 96: 1161-7   DOI   ScienceOn
7 Hwang JH, Yaksh TL: The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. Pain 1997; 70: 15-22   DOI   ScienceOn
8 Rudomin P, Schmidt RF: Presynaptic inhibition in the vertebrate spinal cord revisited. Exp Brain Res 1999; 129: 1-37   DOI
9 Sung KW, Kirby M, McDonald MP, Lovinger DM, Delpire E: Abnormal $GABA_{A}$ receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2C1 cotransporter null mice. J Neurosci 2000; 20: 7531-8   DOI
10 Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355-63   DOI   ScienceOn
11 Malcangio M, Bowery NG: GABA and its receptors in the spinal cord. Trends Pharmacol Sci 1996; 17: 457-62   DOI   ScienceOn
12 Bowery NG: $GABA_{B}$ recepror pharmacology. Annu Rev Pharmacol Toxicol 1993; 33: 109-47   DOI   ScienceOn
13 Sivilotti L, Woolf CJ: The contribution of GABA-A and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol 1994; 72: 169-79   DOI
14 Ibuki T, Hama AT, Wang XT, Pappas GD, Sagen J: Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience 1997; 76: 845-58   DOI   ScienceOn
15 Bennett GJ, Xie YK: A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87-107   DOI   ScienceOn
16 Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353: 1959-64   DOI   ScienceOn
17 Berger A, Dukes EM, Oster G: Clinical characteristics and economic costs of patients with painful neuropathic disorders, J Pain 2004; 5: 143-9   DOI   ScienceOn
18 Eaton MJ, Plunkett JA, Karmally S, Martinez MA, Montanez K: Changes in GAD- and GABA- immunoreactivity in the spinal dorsal horn after peripheral nerve injury and promotion of recovery by lumbar transplant of immortalized serotonergic precursors. J Chem Neuroanat 1998; 16: 57-72   DOI   ScienceOn
19 Polgar E, Gray S, Riddell JS, Todd AJ: Lack of evidence for significant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model. Pain 2004; 111: 144-50   DOI   ScienceOn
20 Carlton SM, Zhou S, Coggeshall RE: Peripheral GABA(A) receptors: evidence for peripheral primary afferent depolarization. Neuroscience 1999; 93: 713-22   DOI   ScienceOn
21 Woolf CJ: Evidence for a centtal component of post-injury pain hypersensitivity. Nature 1983; 306: 686-8   DOI   ScienceOn
22 Teoh H, Malcangio M, Bowery NG: $GABA_{A}$, glutamate and substance P-like immunoreactivity release: effects of novel $GABA_{B}$ antagonists. Br J Pharmacol 1996; 118: 1153-60   DOI   ScienceOn
23 Woolf CJ, Shortland P, Reynolds M, Ridings J, Doubell T, Coggeshall RE: Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy. J Comp Neurol 1995; 360: 121-34   DOI   ScienceOn
24 Willis WD Jr: Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 1999; 124: 395-421   DOI
25 Polgar E, Hughes DI, Riddell JS, Maxwell DJ, Puskar Z, Todd AJ: Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 2003; 104: 229-39   DOI   ScienceOn
26 Fukuoka T, Tokunaga A, Kondo E, Miki K, Tachibana T, Noguchi K: Change in mRNAs for neuropeptides and the GABA(A) receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model. Pain 1998; 78: 13-26   DOI   ScienceOn
27 Desarmenien M, Feltz P, Occhipinti G, Santangelo F, Schlichter R: Coexistence of $GABA_{A}$ and $GABA_{B}$ receptors on A delta and C primary afferents. Br J Pharmacol 1984; 81: 327-33   DOI   ScienceOn
28 Castro-Lopes JM, Malcangio M, Pan BH, Bowery NG: Complex changes of GABAA and GABAB receptor binding in the spinal cord dorsal horn following peripheral inflammation or neurectomy. Brain Res 1995; 679: 289-97   DOI   ScienceOn
29 Sugimoto T, Bennett GJ, Kajander KC: Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. Pain 1990; 42: 205-13   DOI   ScienceOn
30 Moor KA, Kohno T, Karchewski LA, Schilz J, Baba H, Woolf CJ: Partial peripheral nerve injury promotes selective loss of GABAergic inhibition in the supetficial dorsal horn of the spinal cord. J Neurosci 2002; 22: 6724-31   DOI
31 Sivilotti LG, Woolf CJ: The contribution of GABAA and glycine receptots to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neutophysiol 1994; 72: 169-79   DOI
32 Sugimoto T, Bennett GJ, Kajander KC: Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constricrion injury, transection, and strychnine. Pain 1990; 42: 205-13   DOI   ScienceOn
33 Kenshalo DR Jr, Anton F, Dubner R: The detection and perceived intensity of noxious thermal stimuli in monkey and man. J Neutophysiol 1989; 62: 429-36   DOI
34 Palecek J, Paleckova V, Dougherty PM, Carlton SM, Willis WD: Responses of spinothalamic tract cells to mechanical and thermal stimulation of skin in tats with experimental peripheral neuropathy. J Neurophysiol 1992; 67: 1562-73   DOI