title: Peripheral alpha4beta2 nicotinic acetylcholine receptor signalling attenuates tactile allodynia and thermal hyperalgesia after nerve injury in mice.
abstract: OBJECTIVE
  Neuropathic pain is often refractory to conventional analgesics including opioids and non-steroidal anti-inflammatory drugs. Evidence suggests nicotinic acetylcholine receptor ligands regulate pain transmission. Effects of α4β2 nicotinic acetylcholine receptor activation on pain behaviours after nerve injury were studied.
  
  
  METHODS
  Mice were subjected to partial sciatic nerve ligation (PSL). Nicotinic acetylcholine receptor α4 and β2 subunits localization in injured nerves were evaluated by immunohistochemistry. Neuropathic pain, assessed by tactile allodynia and thermal hyperalgesia, was examined by von Frey test and Hargreaves test respectively.
  
  
  RESULTS
  Nicotinic acetylcholine receptor α4 and β2 subunits were up-regulated in injured nerves and were expressed on F4/80-positive macrophages. When nicotine was perineurally administered daily for 4 days (day 7-10; maintenance phase) after nerve injury, pain behaviours were significantly alleviated. The inhibitory effects of nicotine were reversed by co-administration of mecamylamine (non-selective nicotinic acetylcholine receptor antagonist) and dihydro-β-erythroidine (selective α4β2 nicotinic acetylcholine receptor antagonist). Likewise, when α4β2 nicotinic acetylcholine receptor agonists (TC2559 or ABT418) were administered daily for 4 days (day 7-10) after nerve injury, pain behaviours were significantly attenuated. On the other hand, nicotine administered daily for 4 days (day 0-3; initiation phase) after nerve injury alleviated pain behaviours, which were antagonized by co-administration of dihydro-β-erythroidine. TC2559 administered daily for 4 days (day 0-3) also attenuated nerve injury-induced pain behaviours.
  
  
  CONCLUSIONS
  The activation of α4β2 nicotinic acetylcholine receptor expressed on infiltrating macrophages in injured nerves may participate in the relief of PSL-induced neuropathic pain during maintenance and initiation phases.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, Wakayama, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Saika
authors.forename: N
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000175:diagnosis / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000700:Analgesics; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2
keywords: macrophage; nicotine; tactile allodynia; thermal hyperalgesia; α4β2 nAChR