title: Beta2* nicotinic acetylcholine receptors modulate pain sensitivity in acutely abstinent tobacco smokers.
abstract: BACKGROUND
  Nicotine and tobacco smoking administration have demonstrated antinociceptive effects that are mediated by the nicotinic acetylcholine receptor containing the beta2* subunit (beta(2)*-nAChR). In this study, we examined the relationship between beta(2)*-nAChR availability and nociception during acute withdrawal in human tobacco smokers using [(123)I]5-IA-85380 ([(123)I]5-IA) and single photon emission computed tomography (SPECT) brain imaging.
  
  
  METHODS
  Tobacco smokers (n = 24, aged 34 +/- 11 years) participated in the cold pressor task during acute withdrawal (up to 3 hr) and a second cold pressor task following 7-13 days of smoking abstinence on the day they were imaged with [(123)I]5-IA SPECT. The cold pressor task is used to measure pain sensitivity (when subjects first feel pain) and pain tolerance (when subjects cannot withstand pain).
  
  
  RESULTS
  Following 7-13 days of tobacco smoking abstinence, increased pain sensitivity, for example, shorter time to first feel pain, was significantly associated with higher beta(2)*-nAChR availability in the thalamus (r = -.43), parietal (r = -.50), frontal (r = -.55), anterior cingulate (r = -.44), temporal (r = -.43), and occipital (r = -.48) cortices. The percent change in pain sensitivity from the first to second cold pressor task was significantly correlated with beta(2)*-nAChR availability in the thalamus (r = -.57), cerebellum (r = -.50), striatum (r = -.057), parietal (r = -.46), anterior cingulate (r = -.48), temporal (r = -.55), and occipital (r = -.57) cortices. Similar associations were not observed with pain tolerance.
  
  
  CONCLUSIONS
  This suggests that beta(2)*-nAChRs play a role in pain sensitivity but not pain tolerance during tobacco smoking withdrawal. If individuals are more likely to relapse in response to painful stimuli, lower beta(2)*-nAChR availability during acute abstinence may be protective.
authors.affiliation: Yale University School of Medicine and the VA Connecticut Healthcare System, Department of Psychiatry, 116A6, 950 Campbell Avenue, West Haven, CT 06516, USA. kelly.cosgrove@yale.edu
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Sherry
authors.initials: S
authors.lastname: McKee
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Suchitra
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic