Animal pain models

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The use of spinal nerve root ligation in rats is a conventional method for producing allodynia, a cardinal feature of neuropathic pain, and allows the efficacy of pharmacological entities to be assessed as potential antineuro-pathic pain agents. When lidocaine is systemically infused for a defined period of time in rats with surgically induced allodynia, paw-withdrawal thresholds, a measure of allodynia, are increased for the period of infusion when low doses of lidocaine are administered. When larger doses are given, the reduction in allodynia persists well beyond the period of infusion. It has been noted that in some animals a dramatic reduction in allodynia is observed while in others absolutely no effect is generated at all. This parallels human clinical practice closely. An alternative model involves the creation of neuromas in rat sciatic nerves. Electrophysiological measurements can then be made to quantify the amount of spontaneous electrical activity that emanates from the neuroma. Systemic lidocaine almost completely abolishes the spontaneous activity of these neuromas in the absence of nerve conduction blockade.

When given at the right concentrations, systemic lidocaine given to rats prior to the ligation of a sciatic nerve prevents the onset of thermal hyper-algesia. If the lidocaine is given 24 h after the ligation, then the thermal hyperalgesia already present is significantly reduced. Again thinking of rats with induced allodynia, systemic lidocaine causes up to a 66% reduction in tactile allodynia. Remarkably, 21 days after the infusion period, 30-40% of the maximal possible effect on tactile allodynia persists.

The effect of IV lidocaine on allodynia (at least in animal models) seems to fall into three distinct phases. The first is a marked anti-allo-dynic effect during infusion that decreases in the 30-60 min after the cessation of infusion. The second is a transient reduction that occurs in the hours after infusion and the third is a sustained reduction developing in the 24 h after infusion that is maintained over the next 21 days.

It may be that IV lidocaine has effects other than the features of neuropathic pain. When used in animals undergoing colorectal distension, the electrophysiological responses suggest that there is a dose-dependent inhibition of visceromotor and cardiovascular reflexes evoked by colorectal distension suggesting a potentially beneficial effect on visceral pain.

It would seem fair to suggest that the animal evidence is in support of the contention that IV lidocaine can have a pain-relieving effect with the evidence being most robust in the case of neuropathic pain, but with a suggestion that a similar effect may be apparent in the case of visceral pain. Of particular note is that the effect of infusion in animal models can definitely far exceed the duration of infusion and the halflife of the drug, suggesting that the human clinical observation of prolonged relief has a scientific foundation and is not just a form of placebo response.

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