title: Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity.
abstract: OBJECTIVE
  Chronic stress-related conditions are often associated with stress-induced hyperalgesia. However, the neural circuitry responsible for producing stress-induced hyperalgesia is not well characterized. The aim of this study was to determine the contribution of mu-opioid expressing brainstem neurons to the expression of stress-induced hyperalgesia.
  
  
  METHODS
  The present study utilized a model of stress-induced mechanical hypersensitivity that involved application of repeated, light tactile whisker pad stimulation (WPS) in rats. Repeated WPS (10 applications/session, 4 sessions/h in 1 day, sessions on days 1-5 and 8-12) increased defensive-aggressive and hypervigilant behaviors, and produced hypersensitivity to tactile stimulation of the hind paw. In order to test the possible involvement of mu-opioid receptor expressing neurons in the rostral ventral medulla (RVM) to this response, rats received RVM microinjections of the toxin conjugate dermorphin-saporin or its control, saporin. Fourteen days later rats underwent either WPS or sham conditioning.
  
  
  RESULTS
  Repeated WPS produced defensive-aggressive behaviors directed towards the stimulus and mechanical hypersensitivity of the hind paw that persisted for up to 2 weeks after the final WPS session. Dermorphin-saporin, but not saporin, microinjections prevented the development of hind paw mechanical hypersensitivity, but did not affect the defensive-aggressive behaviors.
  
  
  CONCLUSIONS
  The finding that chronic stress produces mechanical hypersensitivity through circuitry that involves the RVM provides a potential neurobiological basis for the complex interaction between chronic stress and pain.
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, 11 Hills Beach Rd, Biddeford, ME 04005, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynolds
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Bilsky
authors.forename: Ian D
authors.initials: ID
authors.lastname: Meng
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D000076985:Saporins; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology; D014110:Touch; D014738:Vibrissae
chemical_list: D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D054789:Ribosome Inactivating Proteins, Type 1; C431163:dermorphin-saporin; D000076985:Saporins