Role of α5-containing nicotinic receptors in neuropathic pain and response to nicotine.
Nicotinic receptors in the central nervous system (nAChRs) are known to play important roles in pain processing and modulate behavioral responses to analgesic drugs, including nicotine. The presence of the α5-neuronal nicotinic accessory subunit in the nicotinic receptor complex is increasingly understood to modulate reward and aversive states, addiction, and possibly pathological pain. In the current study, using α5-knockout (KO) mice and subunit-specific antibodies, we assess the role of α5-containing neuronal nicotinic receptors in neuropathic pain and in the analgesic response to nicotine. After chronic constriction injury (CCI) or partial sciatic nerve ligation (PSNL), no differences in mechanical, heat, or cold hyperalgesia were found in wild-type (WT) versus α5-KO littermate mice. The number of α5-containing nAChRs was decreased (rather than increased) after CCI in the spinal cord and in the thalamus. Nevertheless, thermal analgesic response to nicotine was marginally reduced in CCI α5-KO mice at 4 days after CCI, but not at later timepoints or after PSNL. Interestingly, upon daily intermittent nicotine injections in unoperated mice, WT animals developed tolerance to nicotine-induced analgesia to a larger extent than α5-KO mice. Our results suggest that α5-containing nAChRs mediate analgesic tolerance to nicotine but do not play a major role in neuropathic pain.
Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria. Electronic address: dimitris.xanthos@meduniwien.ac.at.
Dimitris N
DN
Xanthos
Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria.
Johannes W
JW
Beiersdorf
Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria.
Ariane
A
Thrun
Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria.
Bogdan
B
Ianosi
The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Avi
A
Orr-Urtreger
Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria.
Sigismund
S
Huck
Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Austria. Electronic address: petra.scholze@meduniwien.ac.at.
Petra
P
Scholze
D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D059225:Nociception / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology*; D011897:Random Allocation; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism; D014110:Touch
D009538:Nicotine; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C523972:CHRNA5 protein, mouse
Accessory subunit; Central nervous system; Neuropathic; Nicotine; Nicotinic receptor; Pain; Tolerance; α5