title: Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation.
abstract: The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. Lumbar intrathecal injection of (NPY) is antinociceptive, reducing hyper-reflexia to thermal and mechanical stimulation, particularly after nerve injury and inflammation. We have also shown that intrathecal injection of the targeted cytotoxin, Neuropeptide Y-sap (NPY-sap), is also antinociceptive, reducing nocifensive reflex responses to noxious heat and formalin. In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia.
authors.affiliation: Lab of Experimental Neurology, Neurology Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212-2637, USA. eirual14@gmail.com
authors.forename: L L
authors.initials: LL
authors.lastname: Lemons
authors.forename: R G
authors.initials: RG
authors.lastname: Wiley
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000209:etiology; D007249:Inflammation / Q000139:chemically induced; D009020:Morphine / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology
chemical_list: D000700:Analgesics; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D009020:Morphine; D005620:Freund's Adjuvant