Inflammatory hypersensitivity in a rat model of trigeminal neuropathic pain

Thermal and mechanical stimuli have been used to monitor the development of neuropathic pain following an experimental injury to a branch of the trigeminal nerve. However, the response to inflammatory challenge has not been evaluated in a model of orofacial neuropathic pain. The purpose of this study was to determine whether chronic constriction of the infraorbital nerve (IoN) enhances nociceptive responses elicited by the formalin test. The characteristic biphasic response (primarily directed grooming) to formalin injected subcutaneously in the right vibrissae pad was observed in sham-injury rats. Twenty-one days after IoN constriction, formalin injection provoked an immediate response that involved both directed grooming and other abnormal behaviors, e.g. flinching, trismus and shielding of the affected region. As with sham-injury rats, this was followed by a quiescent period and then a second phase of nocifensive behaviors. The total time recorded for all pain-related behaviors was significantly greater in rats with constrictive injuries (P<0.001), due primarily to the exhibition of novel pain-related responses. Histological examination (qualitative) revealed that chronic constriction resulted in a ligature-induced neuroma, as well as a partial denervation of the affected sensory field. Thus, an intense inflammatory hypersensitivity in a rat model of orofacial neuropathic pain develops in association with partial denervation and with an ongoing perineural inflammatory response and neuroma formation.