| First Author | Xanthos DN | Year | 2015 |
| Journal | Neuropharmacology | Volume | 95 |
| Pages | 37-49 | PubMed ID | 25725336 |
| Mgi Jnum | J:315861 | Mgi Id | MGI:6832246 |
| Doi | 10.1016/j.neuropharm.2015.02.012 | Citation | Xanthos DN, et al. (2015) Role of alpha5-containing nicotinic receptors in neuropathic pain and response to nicotine. Neuropharmacology 95:37-49 |
| abstractText | 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 alpha5-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 alpha5-knockout (KO) mice and subunit-specific antibodies, we assess the role of alpha5-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 alpha5-KO littermate mice. The number of alpha5-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 alpha5-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 alpha5-KO mice. Our results suggest that alpha5-containing nAChRs mediate analgesic tolerance to nicotine but do not play a major role in neuropathic pain. |
