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Journal Article
Research Support, Non-U.S. Gov't
Pharmacological studies on a rat model of trigeminal neuropathic pain: baclofen, but not carbamazepine, morphine or tricyclic antidepressants, attenuates the allodynia-like behaviour.
Pain 1999 Februrary
Trigeminal neuralgia is an example of an extreme form of neuropathic pain and continues to be a real therapeutic challenge. Although the pathophysiology of the disorder is uncertain, vascular compression of the trigeminal root resulting in damage to primary afferent neurons is thought to play a major role in the generation of pain. In the present study, we have used a recently developed rat model of trigeminal neuropathic pain, where the neuropathy is produced by a chronic constriction injury of the infraorbital branch of the trigeminal nerve (CCI-ION), and for the first time studied the effects of various pharmacological treatments on this purely sensory model of neuropathic pain. Rats with a CCI-ION consistently display a series of spontaneous behavioural abnormalities that may be indicative of trigeminal paraesthesias/dysesthesias. A hyper-responsiveness of the territory of the ligated infraorbital nerve to light mechanical stimulation with von Frey hairs also develops at 7-12 days after the injury. Pharmacological studies indicated that the mechanical hyper-responsiveness could be reversibly abolished by local injections of alphacaine into the close proximity of the injured nerve. The allodynia-like behaviour was resistant to i.v. morphine. Similarly, single and repeated injections (using the respective T 1/2 as an interval) of tricyclic antidepressants amitriptyline and clomipramine were devoid of effects on the mechanical allodynia-like behaviour. Carbamazepine was effective only after doses (> or =10 mg/kg s.c.) that already caused disturbances in motor co-ordination in the rotarod test. Repeated injections of baclofen (3 mg/kg s.c.) partially alleviated the mechanical allodynia-like behaviour without effects on rotarod performance. The partial anti-allodynic effect of a single injection (5 mg/kg) of baclofen, which was already accompanied by slight motor disturbances, could be antagonized by CGP35348, a selective GABA(B)-receptor antagonist. Functional deficits in the GABAergic system may play an important role in the pathogenesis of this purely sensory rat model of trigeminal neuropathic pain.
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