Peter Spreyer

Pharmacological sensitivity and gene expression analysis of the tibial nerve injury model of neuropathic pain

The tibial nerve injury model is a novel, surgically uncomplicated, rat model of neuropathic pain based on a unilateral transection (neurotomy) of the tibial branch of the sciatic nerve. The aim of the present study was to describe some behavioral and molecular features of the model, and to test its sensitivity to a number of drugs which are currently used for the treatment of neuropathic pain. The model was characterized by a pronounced mechanical allodynia which was present in all subjects and a less robust thermal hyperalgesia. Mechanical allodynia developed within 2 weeks post-surgery and was reliably present for at least 9 weeks. Neurotomized rats showed no autotomy and their body weight developed normally. Gene expression in ipsilateral L5 dorsal root ganglia, analyzed by quantitative polymerase chain reaction (PCR), showed a pronounced up-regulation of galanin and vasointestinal peptide (VIP). This up-regulation developed rapidly (within 1 to 2 days following neurotomy) and remained present for at least 12 days. On the other hand, expression of calcitonin gene-related peptide (CGRP) and substance P mRNA was down-regulated 12 days following neurotomy. Mechanical allodynia was completely reversed by morphine [minimal effective dose (MED): 8 mg/kg, i.p.] and partially reversed by carbamazepine (MED: 64 mg/kg, i.p.), baclofen (MED: 3 mg/kg, i.p.) and amitriptyline (trend for efficacy at 32 mg/kg, i.p.), but not by gabapentin (50-100 mg/kg, i.p.). The finding that the tibial nerve injury model shows a robust and persistent mechanical allodynia which is sensitive to a number of established analgesics, as well as a gene expression profile which is compatible with that obtained in other models of neuropathic pain, further supports its validity as a reliable and surgically uncomplicated model for the study of neuropathic pain.

Metabotropic glutamate mGlu1 receptor mRNA expression in dorsal root ganglia of rats after peripheral nerve injury.

Although cerebral and spinal metabotropic glutamate mGlu(1) receptors are thought to be involved in nociception and in the development/maintenance of chronic pain, it is still unclear to what extent mGlu(1) receptors are present in the dorsal root ganglia of peripheral sensory afferents, and whether their expression is affected during development of chronic pain. It was found in the present study that mGlu(1) receptor messenger RNA (mRNA) is present in rat L5 dorsal root ganglia and that it is strongly downregulated after unilateral axotomy of the tibial branch of the sciatic nerve, a model of chronic neuropathic pain. However, as sham-operated animals showed a similar downregulation, it is suggested that peripheral tissue damage is sufficient to result in a reduction of peripheral mGlu(1) receptor expression.

Molecular Biology of Calcium Channels

Voltage-operated calcium channels (VOCCs) are membrane-spanning multisubunit protein complexes which are the major element controlling calcium entry from the extracellular space into the cytoplasm of excitable cells. VOCCs are predominantly expressed in neuronal and endocrine cells, and in cardiac, smooth, and skeletal muscle.