Trigeminal neuropathic pain: Study of the effects of behavioral, pharmacological and surgical manipulations in a rat model.

摘要

Neuropathic pain refers to pain syndromes resulting from damage or dysfunction of the somatosensory nervous system. It is considered to be very resistant to common painkillers and patients often suffer from terrible discomfort. Trigeminal neuralgia (TN) is an extreme form of facial neuropathic pain. To meet the specificity of trigeminal neuropathic pain syndromes, a rat model was developed whereby the Infraorbital nerve (IoN), which constitutes almost the entire maxillary branch of the trigeminal nerve, is loosely ligated (CCI). Following IoN surgery, rats display increased face grooming behavior directed to the territory of the injured IoN indicative of spontaneous pain. After an initial period of hyporesponsiveness, rats also become hyperresponsive to mechanical stimulation of the IoN territory.; In a series of methodological studies, aimed at further validating and improving the usefulness of the IoN model, it was found that an important distinction should be made between face grooming during body grooming, which is part of normal grooming behavior and which remains unaltered by IoN surgery, and isolated face grooming, which is specifically related to IoN-CCI induced spontaneous pain. It was also found that neither IoN transection nor tight ligation produce similar behavioral changes. Finally, in an attempt to reduce variability between rats, it was found that bilateral IoN surgery drastically increases the amount of isolated face grooming compared to unilaterally ligated animals. However, this increase was accompanied with an equivalent increase in variation.; A series of pharmacological studies was performed where the effects of existing analgesics were compared to those of newly developed 5-HT1A receptor agonists, F 13640 and F 13714. It was found that carbamazepine, the first-line drug against TN, F 13640 and F 13714, but not morphine or baclofen, significantly reduce IoN-CCI induced isolated face grooming behavior. It was also found that morphine, baclofen and the F compounds significantly reduce mechanical hyperresponsiveness following acute and chronic administration.; The results support the validity of isolated face grooming and responses to von Frey filament stimulation as behavioral measures of IoN-CCI induced neuropathic pain. The effects of the 5-HT1A receptor agonists confirm recent evidence proposing 5-HT1A receptor activation as a new molecular mechanism of analgesia against nociceptive and neuropathic pain.