The role of the GABA-A receptor of the adjacent intact dorsal root ganglion neurons in rats with neuropathic pain

• Autorzy: Ran R. , Gu J. , Fu J. , Zhong H. , Zhao Y. , Gu Y. C. , Zhang A. , Li G. , Wang L. , Wang Q.
• Języki publikacji: EN

Abstrakty

EN

We aim to investigate the changes of The y-aminobutyric acid (GABA) signals in the adjacent intact dorsal root ganglion (DRG) and the contribution of these changes to the development and maintenance of neuropathic pain (NPP). After establishment of neuropathic pain model with the lumbar 5 spinal nerve ligation (L5 SNL), the GABA-evoked currents were recorded in the acutely dissociated L4 DRG neurons using whole-cell patch clamp. Moreover, Muscimol or Bicuculline were respectively topically injected to the L4 DRG at the time of nerve injury and post-operative 5 days (POD5). The pain thresholds of hind paw were recorded. We found that the incidence and amplitude of GABA currents significantly decreased in the large and medium L4 DRG neurons after SNL (P<0.05). Furthermore, in the L5 SNL rats, 20 ug Muscimol injected immediately after injury caused a long-lasting attenuation of mechanical allodynia (P<0.05), whereas the thermal hyperalgesia was not alleviated (P>0.05). 0.15 ug Bicuculline further decreased the pain thresholds (P<0.05) and reversed the pain-alleviating effects of Muscimol. However, at POD5, 20 ug Muscimol only exhibited transient alleviating effects (P<0.05). In conclusion, the decrease of inhibition signal mediated by GABA-A receptor in the adjacent intact DRG neurons may be crucial in the development of hyperalgesia in NPP.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2014
• Tom: 74
• Numer: 4
• Opis fizyczny: p.405-414,fig.,ref.

Twórcy

autor

Ran R.

• Renmin Hospital, Hubei University of Medicine, Shiyan, China

autor

Gu J.

• Renmin Hospital, Hubei University of Medicine, Shiyan, China

autor

Fu J.

• Renmin Hospital, Hubei University of Medicine, Shiyan, China

autor

Zhong H.

• Renmin Hospital, Hubei University of Medicine, Shiyan, China

autor

Zhao Y.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

autor

Gu Y. C.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

autor

Zhang A.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

autor

Li G.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

autor

Wang L.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

autor

Wang Q.

• Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Bibliografia

• Enna SJ, McCarson KE (2006) The role of GABA in the mediation and perception of pain. Adv Pharmacol 54: 1-27.
• Gilron I, Jensen TS, Dickenson AH (2013) Combination pharmacotherapy for management of chronic pain: from bench to bedside. Lancet Neurol 12: 1084-1095.
• Harper AA, Lawson SN (1985) Conduction velocity is related to morphological cell type in rat dorsal root gan¬glion neurons. J Physiol (Lond) 359: 31-46.
• Jang JH, Kim KH, Nam TS, Lee WT, Park KA, Kim D-W, Leem JW (2007a) The role of uninjured C-afferents and injured afferents in the generation of mechanical hypersensitivity after partial peripheral nerve injury in the rat. Experimental Neurology 204: 288-298.
• Jang JH, Kim KH, Nam TS, Lee WT, Park KA, Kim DW, Leem JW (2007b) The role of uninjured C-afferents and injured afferents in the generation of mechanical hyper- sensitivity after partial peripheral nerve injury in the rat. Exp Neurol 204: 288-298.
• Ji G, Zhou S, Kochukov MY, Westlund KN, Carlton SM (2007) Plasticity in intact A[delta]- and C-fibers contrib¬utes to cold hypersensitivity in neuropathic rats. Neuroscience 150: 182-193.
• Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355-363.
• Labrakakis C, Tong CK, Weissman T, Torsney C, MacDermott AB (2003) Localization and function of ATP and GABAA receptors expressed by nociceptors and other postnatal sensory neurons in rat. J Physiol 549: 131-142.
• Li GH, Guan BC, Li ZW (2005) Effects of dopamine, SKF- 38393 and R(-)-NPA on ATP-activated currents in rat DRG neurons. Can J Physiol Pharmacol 83: 267-277.
• Liu J, Wolfe D, Hao S, Huang S, Glorioso JC, Mata M, Fink DJ (2004) Peripherally delivered glutamic acid decar- boxylase gene therapy for spinal cord injury pain. Mol Ther 10: 57-66.
• Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EO, Larsen JS, Ahring PK, Mirza NR (2008) Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1- hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl- 2-carbonitr ile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 327: 969-981.
• Naik AK, Pathirathna S, Jevtovic-Todorovic V (2008) GABAA receptor modulation in dorsal root ganglia in vivo affects chronic pain after nerve injury. Neuroscience 154: 1539-1553.
• Naik AK, Latham JR, Obradovic A, Jevtovic-Todorovic V (2012) Dorsal root ganglion application of muscimol prevents hyperalgesia and stimulates myelin protein expression after sciatic nerve injury in rats. Anesth Analg 114: 674-682.
• Nickel FT, Seifert F, Lanz S, Maihöfner C (2012) Mechanisms of neuropathic pain. Eur Neuropsychopharmacol 22: 81-91.
• Nishi S, Minota S, Karczmar AG (1974) Primary afferent neurones: The ionic mechanism of GABA-mediated depolarization. Neuropharmacology 13: 215-219.
• Obata K, Yamanaka H, Fukuoka T, Yi D, Tokunaga A, Hashimoto N, Yoshikawa H, Noguchi K (2003) Contribution of injured and uninjured dorsal root gangli¬on neurons to pain behavior and the changes in gene expression following chronic constriction injury of the sciatic nerve in rats. Pain 101: 65-77.
• Price TJ, Cervero F, Gold MS, Hammond DL, Prescott SA (2009) Chloride regulation in the pain pathway. Brain Res Rev 60: 149-170.
• Puljak L, Kojundzic SL, Hogan QH, Sapunar D (2009) Targeted delivery of pharmacological agents into rat dorsal root ganglion. J Neurosci Methods 177: 397¬402.
• Shehab SAS, Al-Marashda K, Al-Zahmi A, Abdul-Kareem A, Al-Sultan MAH (2008) Unmyelinated primary affer¬ents from adjacent spinal nerves intermingle in the spinal dorsal horn: A possible mechanism contributing to neuro¬pathic pain. Brain Res 1208: 111-119.
• Shim B, Kim DW, Kim BH, Nam TS, Leem JW, Chung JM (2005) Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropa¬thy. Neuroscience 132: 193-201.
• Xiong YC, Li XM, Wang XJ, Liu YQ, Qiu F, Wu D, Gan YB, Wang BH, Hu WP (2010) Prokineticin 2 suppresses GABA-activated current in rat primary sensory neurons. Neuropharmacology 59: 589-594.
• Zeilhofer HU, Möhler H, Di Lio A (2009) GABAergic anal¬gesia: new insights from mutant mice and subtype-selec¬tive agonists. Trends Pharmacol Sci 30: 397-402.