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Secondary hyperalgesia in the monoarthritic rat is mediated by GABAB and NK1 receptors of spinal dorsal horn neurons: a behavior and c-fos study.

Author	A R Castro, M Pinto, D Lima, I Tavares
Citation Information	Neuroscience, 141:2087-95 (2006)
Keywords	Animals, Arthritis, Baclofen, Behavior, Animal, Drug Interactions, GABA Agonists, Gene Expression, Hyperalgesia, Immunohistochemistry, Male, Pain Measurement, Pain Threshold, Proto-Oncogene Proteins c-fos, Rats, Rats, Wistar, Receptors, GABA-B, Receptors, Neurokinin-1, Ribosome Inactivating Proteins, Type 1, Substance P
Related Products	AB5060
Pub Med ID	16809001

Secondary hyperalgesia in the monoarthritic rat is accompanied by a decrease in nociceptive activation of spinal neurons expressing GABA(B) receptors and by the opposite effect in the cells expressing neurokinin 1 (NK1)-receptors. In order to ascertain the relative role of each receptor, the effects of intrathecal administration of SP-saporin (SP-SAP), baclofen or both were evaluated, using a model of secondary hyperalgesia that consists of mechanical stimulation of the hindlimb skin close to an inflamed joint. Four days after the induction of monoarthritis by intraarticular injection of Complete Freund's Adjuvant (CFA), a cannula was implanted at T(13)-L(1) level and 10 microl of saline or SP-SAP (10(-6) M) were intrathecally (i.t.) injected. Fourteen days after CFA-injection, half of the animals from each group received i.t. injections of 10 microl saline and the remainder were injected with the same volume of baclofen (1 microg). Ten minutes later, the animals were behaviorally evaluated by the von Frey test or submitted to noxious mechanical stimulation to analyze c-fos expression. The von Frey thresholds increased after the treatments, but more pronouncedly after baclofen or SP-SAP plus baclofen. In segments L(2)-L(3), the spinal area that receives input from the stimulated skin close to the inflamed joint, the numbers of Fos-immunoreactive neurons were reduced after the three treatments both in the superficial and deep dorsal horn. In segments T(13)-L(1), the numbers of Fos-immunoreactive neurons were significantly reduced after treatment with SP-SAP plus baclofen in both dorsal horn regions, and in the deep dorsal horn after baclofen treatment. We conclude that both GABA(B) and NK1 receptors of spinal dorsal horn neurons participate in secondary hyperalgesia in the monoarthritic rat, although the decrease in GABA inhibition appears to play a more important role than the increase in SP-mediated effects.