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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. 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 SpragueβDawley male rats.
Among antidepressants currently used as first line treatment of chronic neuropathic pain, tricyclics, such as amitriptyline, and mixed inhibitors of noradrenaline NA and serotonin 5-HT re-uptake, such as duloxetine and venlafaxine, are the most frequently prescribed. Accordingly, agomelatine has the potential to become a novel antidepressant drug of clinical interest for a better treatment of neuropathic pain in humans.
These data led us to assess whether or not the anti-neuropathic pain properties of agomelatine evidenced at somatic hindpaw level could also be demonstrated at cephalic level. To this goal, we investigated possible changes by this drug of mechanical allodynia induced by infraorbital nerve ligation compared to sciatic nerve ligation in rats. Finally, because neurochemical and electrophysiological investigations showed that agomelatine treatment may affect both NA and 5-HT neurotransmissions Millan et al.
After surgery, all efforts were made to minimize suffering. In particular, nerve-ligated rats were housed under the very same conditions, except that each cage was for only three operated rats, so as to avoid as much as possible allodynic contacts between them.
