RESUMEN
PURPOSE: Due to the difficulty of using neural tracers in humans, knowledge of the nociceptive system's anatomy is mainly derived from studies in animals and mainly in rats. The aim of this study was to investigate the morphological differences of the ascending spinal nociceptive pathways between the rat and the macaque monkey; in order to evaluate the variability of this anatomy during phylogenesis, and thus to know if the anatomical description of these pathways can be transposed from the rat to the human. METHODS: A review and analysis of the literature were performed. The criteria used for comparison were: origins, pathways, their terminations in target structures, and projections from target structures of ascending spinal nociceptive pathways. The monkey was used as an intermediate species for comparison because of the lack of data in humans. The hypothesis of transposition of anatomy between rat and human was considered rejected if differences were found between rat and monkey. RESULTS: An anatomical difference in termination was found for the spino-annular or spino-periaqueductal grey (spino-PAG) pathway and transposition of its anatomy from rat to human was rejected. No difference was found in other pathways and the transposition of their anatomy from rat to human was therefore, not rejected. CONCLUSION: This work highlights the conservation of most of the ascending spinal nociceptive pathways' anatomy between rat and monkey. Thus, the possibility for a transposition of their anatomy between rat and human is not rejected.
RESUMEN
Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans which are less effective against cephalic neuropathic pain. Whether this also applies to the antidepressant agomelatine, with its unique pharmacological properties as MT1/MT2 melatonin receptor agonist and 5-HT2B/5-HT2C serotonin receptor antagonist, has been investigated in two rat models of neuropathic pain. Acute treatments were performed 2 weeks after unilateral chronic constriction (ligation) injury to the sciatic nerve (CCI-SN) or the infraorbital nerve (CCI-ION), when maximal mechanical allodynia had developed in ipsilateral hindpaw or vibrissal pad, respectively, in Sprague-Dawley male rats. Although agomelatine (45 mg/kg i.p.) alone was inactive, co-treatment with gabapentin, at an essentially ineffective dose (50 mg/kg i.p.) on its own, produced marked anti-allodynic effects, especially in CCI-ION rats. In both CCI-SN and CCI-ION models, suppression of mechanical allodynia by 'agomelatine + gabapentin' could be partially mimicked by the combination of 5-HT2C antagonist (SB 242084) + gabapentin, but not by melatonin or 5-HT2B antagonist (RS 127445, LY 266097), alone or combined with gabapentin. In contrast, pretreatment by idazoxan, propranolol or the ß2 antagonist ICI 118551 markedly inhibited the anti-allodynic effect of 'agomelatine + gabapentin' in both CCI-SN and CCI-ION rats, whereas pretreatment by the MT1/MT2 receptor antagonist S22153 was inactive. Altogether these data indicate that 'agomelatine + gabapentin' is a potent anti-allodynic combination at both cephalic and extra-cephalic levels, whose action implicates α2- and ß2-adrenoreceptor-mediated noradrenergic neurotransmission.
