Impact of chronic nicotine on the development and maintenance of neuropathic hypersensitivity in the rat.

Rationale: Clinical data support a correlation between smoking and the incidence and severity of some chronic pain conditions. However, the impact of nicotine on neuropathic pain has been largely ignored in the laboratory setting.

Objectives: The purpose of these studies was to determine if chronic nicotine would alter mechanical hypersensitivity after spinal nerve ligation.

Spinal cord dynorphin expression increases, but does not drive microglial prostaglandin production or mechanical hypersensitivity after incisional surgery in rats.

Spinally released dynorphin contributes to hypersensitivity from nerve injury, inflammation, and sustained morphine treatment, but its role in post-operative pain has not been tested. Intrathecal injection of dynorphin activates cyclooxygenase (COX)-1 and -2 to induce hypersensitivity. Spinal COX-1 expression and activity increase following incisional paw surgery in rats, although the stimulus for this increase is not known.

Knock down of the alpha 5 nicotinic acetylcholine receptor in spinal nerve-ligated rats alleviates mechanical allodynia.

Nicotinic acetylcholine receptor (nAChR) agonists are known to alleviate neuropathic and inflammatory pain via activation of a heterogeneous population of receptors. However, the function of nAChRs in the maintenance of neuropathic pain is not known. Spinal nerve ligation (SNL) increases the spinal expression of the alpha5 nAChR subunit ipsilateral to injury.

Immunocytochemical localization of the alpha3, alpha4, alpha5, alpha7, beta2, beta3 and beta4 nicotinic acetylcholine receptor subunits in the locus coeruleus of the rat.

The presence of nicotinic acetylcholine receptors (nAChRs) within the locus coeruleus (LC) has been examined using a wide range of techniques. However, the expression pattern of individual nicotinic receptor subunits has not been described. Using immunocytochemistry, we demonstrate the distribution of the alpha3, alpha4, alpha5, alpha7, beta2, beta3 and beta4 nAChR subunits within the LC.