strychnine and Peripheral-Nervous-System-Diseases

Taurine is an inhibitory amino-acid which has been proposed as a nociceptive process neuromodulator. The glycine(A) receptor (glyR(A)) has been postulated as a receptor in which taurine exerts its function. Functional image studies have documented the role of the anterior cingulate cortex (ACC) in the affective component of pain. The aim of this study was to investigate the role of taurine as a glycinergic agonist in the ACC using a neuropathic pain model related to autotomy behaviour (AB). In order to test whether glyR(A) is responsible for taurine actions, we microinjected strychnine, a glyR(A) antagonist. We used taurine microinjected into the ACC, followed by a thermonociceptive stimulus and a sciatic denervation. Chronic nociception was measured by the autotomy score, onset and incidence. The administration of taurine 7 days after denervation modifies the temporal course of AB by inhibiting it. Our results showed a decreased autotomy score and incidence in the taurine groups, as well as a delay in the onset. Those experimental groups in which strychnine was microinjected into the ACC, either on its own or before the microinjection of taurine, showed no difference as compared to the control group. When taurine was microinjected prior to strychnine, the group behaved as if only taurine had been administered. Our results evidence a significant neuropathic nociception relief measured as an AB decrease by the microinjection of taurine into the ACC. Besides, the role of the glyR(A) is evidenced by the fact that strychnine antagonises the antinociceptive effect of taurine.

Topics: Animals; Behavior, Animal; Glycine Agents; Gyrus Cinguli; Male; Microinjections; Pain; Pain Measurement; Peripheral Nervous System Diseases; Rats; Rats, Wistar; Receptors, Glycine; Strychnine; Taurine

Changes in neuronal excitability due to increase in excitatory transmitters and/or removal of local inhibition underlie central neuron sensitization and altered responsiveness related to painful sensory disorders. To distinguish the contribution of each of the two mechanisms, they have been mimicked separately in intact rats, by iontophoretically applying excitatory (NMDA) and disinhibitory (the glycine antagonist strychnine) substances during dorsal horn neuron recording. Wide dynamic range (WDR) neurons were extracellularly recorded at the L5-L6 lumbar level in anesthetized and paralyzed rats and an analysis was made, before and during the substance application, of the characteristics of the response to noxious stimuli applied to areas supplied by the ipsilateral sciatic nerve and the contralateral sciatic and saphenous nerves ("inappropriate" areas). The results show that the neuronal response properties were modified differently during the NMDA-induced hyperexcitability and strychnine-induced release of inhibition. Both manipulations brought about the unmasking of responses to previously ineffective, noxious stimuli applied to the contralateral sciatic and saphenous nerve areas, and the enhancement of the responses to noxious stimulation of the ipsilateral sciatic nerve area. However, it was only during the increased excitation induced by NMDA that the neurons exhibited hyperresponsiveness, with long-lasting afterdischarge, to noxious stimulation of the ipsi- and contralateral areas. Such response features resemble those described in sensitized neurons in neuropathic rats and associated with behavioral signs of hyperalgesia. This suggests, by inference, a crucial contribution of the NMDA-induced increased excitability to the expression of neuronal sensitization related to this painful sensory disorder.

Topics: Animals; Excitatory Amino Acid Agonists; Glycine Agents; Hyperalgesia; Male; N-Methylaspartate; Neurons, Afferent; Pain; Peripheral Nervous System Diseases; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Sensation Disorders; Strychnine

A painful peripheral neuropathy was produced by loosely tying constrictive ligatures around the sciatic nerve of rats. Eight days after the nerve injury and after a series of injections a subconvulsive dose of strychnine, the animals were sacrificed and the spinal cord dorsal horn was examined for signs of transsynaptic degeneration. The presence of strychnine-enhanced transsynaptic degeneration was apparent from the presence of many pyknotic and hyperchromatic neurons (dark neurons). The dark neurons were seen in laminae I-IV bilaterally, but they were significantly more frequent ipsilateral to the nerve injury. The majority of the dark neurons were found within the medial two-thirds of laminae I-II; this region corresponds to the intraspinal territory of the sciatic nerve's small diameter afferents. The results suggest that a peripheral nerve injury that produces neuropathic pain induces morphological alterations of intraspinal somatosensory circuitry.

Topics: Animals; Male; Nerve Degeneration; Pain; Peripheral Nervous System Diseases; Rats; Rats, Inbred Strains; Strychnine