Pain
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Neuropathic pain, due to peripheral nerve damage, can include allodynia (perception of innocuous stimuli as being painful), hyperalgesia (increased sensitivity to noxious stimuli) and spontaneous pain, often accompanied by sensory deficits. Plasticity in transmission and modulatory systems are implicated in the underlying mechanisms. The Kim and Chung rodent model of neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of the sciatic nerve and reproducibly induced mechanical and cold allodynia in the ipsilateral hindpaw over the 14 day post-operative period. ⋯ After neuropathy the potency of omega-conotoxin-GVIA was increased at lower doses in comparison to control. This indicates an altered role for N-type but not P-type VDCCs in sensory transmission after neuropathy and selective plasticity in these channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important.
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The present study aimed to elucidate the distribution of gamma-aminobutyric acid (GABA) transporters in the spinal trigeminal nucleus after carrageenan injections. Dense GAT-1 and GAT-3 but very little GAT-2 immunoreactivity was observed in the normal rat spinal trigeminal nucleus. The GAT-1-positive glial cells in the normal rat spinal trigeminal nucleus contained dense bundles of glial filaments and had features of astrocytes. ⋯ Electron microscopy showed that transporter immunoreactivity in the spinal trigeminal nucleus of carrageenan-injected rats was predominantly present in glial processes, showing that the increase in the number of processes observed at light microscopy was due to increased immunoreactivity in glial processes. An increased expression of GABA transporters in the carrageenan-injected spinal trigeminal nucleus could therefore result in a faster removal of GABA from the synaptic cleft of GABAergic axon terminals compared to normal rats. This could result in reduced inhibition/increased activity of the trigeminothalamic neurons in the spinal trigeminal nucleus, and could contribute to hyperalgesia after carrageenan injections.
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We have examined the effects of cannabinoid agonists on hyperalgesia in a model of neuropathic pain in the rat and investigated the possible sites of action. The antihyperalgesic activity of the cannabinoids was compared with their ability to elicit behavioural effects characteristic of central cannabinoid activity. WIN55,212-2 (0.3-10 mg kg(-1)), CP-55,940 (0.03-1 mg kg(-1)) and HU-210 (0.001-0.03 mg kg(-1)) were all active in a 'tetrad' of tests consisting of tail-flick, catalepsy, rotarod and hypothermia following subcutaneous administration, with a rank order of potency in each of HU-210 > CP-55,940 > WIN55,212-2. ⋯ The antihyperalgesic effect of WIN55,212-2 injected into the ipsilateral paw was blocked by subcutaneously administered SR141716A, but was not affected by intrathecally administered SR141716A. These data show that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via an action in both the CNS and in the periphery.
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We investigated the effects of acute and chronic tramadol treatment on T lymphocyte function and natural killer (NK) cell activity in rats receiving chronic constriction injury (CCI) of the sciatic nerve. T lymphocyte function was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (PHA)-induced splenocyte proliferation. NK cell activity was measured by lactic acid dehydrogenase release assay. ⋯ However, the activity of splenocyte proliferation was decreased in the 80 mg/kg per day group when compared with the saline and 40 mg/kg per day groups. These data suggest that tramadol treatment has an immunological profile different from pure mu-opioid agonists like morphine, which is known to suppress both NK cell activity and T lymphocyte proliferation at a subanalgesic dose in CCI rats. Considering analgesic and immunosuppressive effects, tramadol treatment may be a better choice than morphine for treatment of chronic neuropathic pain, particularly in patients with compromised immunity.