A characteristic symptom of neuropathic pain is mechanical allodynia. In animal models of neuropathic pain, mechanical allodynia is often assessed using von Frey filaments. Although the forces applied with these filaments are highly reproducible, there are various disadvantages of using this method. Testing paradigms and definitions of withdrawal threshold are not standardised. Moreover, measurements may be influenced by various conditions, such as ambient temperature, humidity, weight bearing of the limb and stress. We have therefore investigated another technique to assess mechanical allodynia, the 'CatWalk' automated quantitative gait analysis. With this computer-assisted method of locomotor analysis, it is possible to objectively and rapidly quantify several gait parameters, including duration of different phases of the step cycle and pressure applied during locomotion. We tested rats with a chronic constriction injury of the sciatic nerve, a model of neuropathic pain, both with von Frey filaments and the CatWalk method. We demonstrate that these rats minimise contact with the affected paw during locomotion, as demonstrated by a reduction in stance phase and pressure applied during stance. Moreover, these parameters show a high degree of correlation with mechanical withdrawal thresholds as determined by von Frey filaments. We therefore suggest that the CatWalk method might serve as an additional tool in the investigation of mechanical allodynia.

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The presence of both pro-opiomelanocortin-derived peptides and melanocortin (MC) receptors in nociception-associated areas in the spinal cord suggests that, at the spinal level, the MC system might be involved in nociceptive transmission. In the present study, we demonstrate that a chronic constriction injury (CCI) to the rat sciatic nerve, a lesion that produces neuropathic pain, results in changes in the spinal cord MC system, as shown by an increased binding of 125 I-NDP-MSH to the dorsal horn. Furthermore, we investigated whether intrathecal administration (in the cisterna magna) of selective MC receptor ligands can affect the mechanical and cold allodynia associated with the CCI. Mechanical and cold allodynia were assessed by measuring withdrawal responses of the affected limb to von Frey filaments and withdrawal latencies upon immersion in a 4.5°C water bath, respectively. We show that treatment with the MC receptor antagonist SHU9119 has a profound anti-allodynic effect, suggesting that the endogenous MC system has a tonic effect on nociception. In contrast, administration of the MC4 receptor agonists MTII and D-Tyr-MTII primarily increases the sensitivity to mechanical and cold stimulation. No antinociceptive action was observed after administration of the selective MC3 receptor agonist Nle-␥-MSH. Together, our data suggest that the spinal cord MC system is involved in neuropathic pain and that the effects of MC receptor ligands on the responses to painful stimuli are exerted through the MC4 receptor. In conclusion, antagonism of the spinal melanocortin system might provide a new approach in the treatment of neuropathic pain. Key words: neuropathic pain; chronic constriction injury; allodynia; melanocortins; melanocortin-4 receptor; spinal cord; dorsal horn; in situ 125 I-NDP-MSH bindingIn humans, damage to the nervous system (a peripheral nerve, dorsal root ganglion, dorsal root, or the CNS) can lead to a pain state referred to as neuropathic pain. This syndrome is characterized by spontaneous pain in combination with allodynia (pain evoked by normally nonpainful stimuli) and hyperalgesia (an increased response to painful stimuli). In current clinical practice, several drugs are used to control neuropathic pain, including tricyclic antidepressants (for review, see Ollat and Cesaro, 1995;Kingery, 1997), anticonvulsants (Rosenberg et al., 1997), systemic administration of local anesthetics (Glazer and Portenoy, 1991;Rowbotham et al., 1991), and NMDA receptor antagonists (Backonja et al., 1994;Felsby et al., 1996). Despite this wide range of drugs, the treatment of neuropathic pain is often unsatisfactory and limited by the occurrence of adverse side effects. Over the past decade, a number of animal models of neuropathic pain have become available, producing symptoms that closely resemble those observed in human neuropathic pain. Research using these preclinical models has yielded an array of potential new analgesics, including different enzyme inhibitors, ion channel blockers, and ligands for various rece...

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In this study we demonstrated that continuous intrathecal infusion of the melanocortin-receptor antagonist SHU9119 reduces cold and mechanical allodynia in rats with a chronic constriction injury of the sciatic nerve, a lesion producing neuropathic pain.