title: De novo expression of neurokinin-1 receptors by spinoparabrachial lamina I pyramidal neurons following a peripheral nerve lesion.
abstract: Lamina I of the spinal dorsal horn is a major site of integration and transmission to higher centers of nociceptive information from the periphery. One important primary afferent population that transmits such information to the spinal cord expresses substance P (SP). These fibers terminate in contact with lamina I projection neurons that express the SP receptor, also known as the neurokinin-1 receptor (NK-1r). Three types of lamina I projection neurons have been described: multipolar, fusiform, and pyramidal. Most neurons of the first two types are thought to be nociceptive and express the NK-1r, whereas most pyramidal neurons are nonnociceptive and do not express the NK-1r. In this immunocytochemical and behavioral study, we induced a neuropathic pain-like condition in the rat by means of a polyethylene cuff placed around in the sciatic nerve. We document that this lesion led to a de novo expression of NK-1r on pyramidal neurons as well as a significant increase in SP-immunoreactive innervation onto these neurons. These phenotypic changes were evident at the time of onset of neuropathic pain-related behavior. Additionally, we show that, after a noxious stimulus (intradermal capsaicin injection), these NK-1r on pyramidal neurons were internalized, providing evidence that these neurons become responsive to peripheral noxious stimulation. We suggest that the changes following nerve lesion in the phenotype and innervation pattern of pyramidal neurons are of significance for neuropathic pain and/or limb temperature regulation.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Abeer W
authors.initials: AW
authors.lastname: Saeed
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-da-Silva
mesh_terms: D000818:Animals; D001917:Brachial Plexus / Q000166:cytology*; D001933:Brain Stem / Q000166:cytology; D002211:Capsaicin / Q000494:pharmacology; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000473:pathology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*; D013373:Substance P / Q000378:metabolism
chemical_list: D018040:Receptors, Neurokinin-1; D013373:Substance P; D002772:Cholera Toxin; D002211:Capsaicin