Antihyperalgesic effects of clomipramine and tramadol in a model of posttraumatic trigeminal neuropathic pain in mice.

AIMS: To develop a behavioral model in mice that is capable of mimicking some distinctive symptoms of human posttraumatic trigeminal neuropathic pain such as spontaneous pain, cold allodynia, and chemical÷inflammatory hyperalgesia, and to use this model to investigate the antinociceptive effects of clomipramine and tramadol, two drugs used for the treatment of neuropathic pain. METHODS: A partial tight ligature of the right infraorbital nerve by an intraoral access or a sham procedure was performed. Fourteen days later, mice were subcutaneously injected with saline or drugs and the spontaneous nociceptive behavior, as well as the responses to topical acetone and to formalin or capsaicin injected into the ipsilateral vibrissal pad, were assessed. Data were analyzed by ANOVA. RESULTS: Neuropathic mice exhibited an increased spontaneous rubbing÷scratching of the ipsilateral vibrissal pad, together with enhanced responses to cooling (acetone) and the chemical irritants (formalin, capsaicin). Clomipramine and tramadol produced an antihyperalgesic effect on most of these nociceptive responses, but tramadol was ineffective on capsaicin-induced hyperalgesia. CONCLUSION: Nociceptive responses in this neuropathic pain model in mice exhibited a pattern consistent with the pain described by posttraumatic trigeminal neuropathic patients. The selective antihyperalgesic effect obtained with two commonly used drugs for treating neuropathic pain confirms the validity of this preclinical model.

The action of topical basic fibroblast growth factor in facial nerve regeneration.

OBJECTIVE: To analyze the influence of the topical use of basic fibroblast growth factor (bFGF) in the regeneration of the facial nerve in rats. STUDY DESIGN: Experimental study. MATERIALS AND METHODS: Twenty-eight Wistar adult male rats underwent complete section of the facial nerve trunk, followed by end-to-end anastomosis with epineural sutures. An osmotic minipump equipped with a delivery catheter was implanted subcutaneously near the neural anastomosis. During the subsequent 14 days, 14 animals received a solution containing 25 microg/ml of bFGF, 250 UI/ml of sodium heparin, and 1,000 microg/ml of human albumin diluted in Ringer lactate, and 14 animals received a control solution of the same components without bFGF. To evaluate facial nerve regeneration, the number of myelinated fibers evident on histologic sections was counted on the 14th (7 experimental and 8 control animals) and the 28th days (7 experimental and 6 control animals) after surgery, and the facial movements of vibrissae and the blink reflex were evaluated on alternate days until the 28th day. RESULTS: On histologic evaluation, the number of myelinated fibers was similar between groups on the 14th day and greater in the group that received bFGF on the 28th day. Behavioral evaluation showed that the animals of the bFGF group presented better functional results between the 6th and 16th days for the blink test and the 14th to the 16th days for vibrissae movements. CONCLUSION: This study showed that the regeneration of the facial nerve occurred earlier and resulted in significantly more myelinated nerve fibers in the animals that received topical bFGF.

Blockage of vibrissal afferents: III. Electrocorticographic effects.

We have shown signs of behavioral depression after vibrissal deafferentation. Locomotor slowing, motor impairments and footshock thresholds increment were demonstrated after vibrissal afferent blockages. Here, we study the electrocortical (ECoG) effects of vibrissal pad anaesthesia, also replicated by bilateral brachial plexus blockage. We found in both cases, that this acute and massive deafferentation produces synchronization over the entire neocortex accompanied by an important loss of muscular electrical activity. Slow waves observed in this condition were similar to those recorded in the sleeping rat without any treatment, but in our case, there were no behavioral signs of sleep. Thus a clear behavioral electroencephalographic dissociation was obtained by acute deafferentation. These results would seem to support the sleep deafferentation hypothesis.