Involvement of spinal Met-enkephalin in nicotine-induced antinociception in mice.
Nicotine is neuronal stimulating drug in the central nervous system and elicits various effects through nicotinic acetylcholine receptors. As previously reported, nicotine has an antinociceptive effect through activation of endogenous opioid neurons. However, detailed mechanisms of nicotine-induced antinociception are uncertain. In this study, we focused on spinal cord and investigated the involvement of endogenous opioidergic neurons in nicotine-induced antinociception in mice. In the tail-pinch test, subcutaneously administered nicotine (5 mg/kg) produced maximal antinociception 0.5 h after nicotine administration; this was attenuated by mecamylamine (MEC, 3 mg/kg, s.c.) or naloxone (NLX, 1 mg/kg, s.c.) administration. Intrathecal nicotine (10 mug) produced maximal antinociception at 2 min and this was also attenuated by MEC (3 mg/kg, s.c.) or NLX (1 mg/kg, s.c.) administration. The preproenkephalin (ppENK) mRNA level in spinal cord, but not dorsal root ganglion, was significantly increased 2 h following nicotine administration and recovered to control level 4 h after nicotine (5 mg/kg, s.c.) administration. This increase in ppENK mRNA level was inhibited by MEC (3 mg/kg, s.c.). The mRNA levels of preprodynorphin and preproopiomelanocortin were not increased by nicotine (5 mg/kg, s.c.). In the dorsal horn of the lumbar spinal cord, methionine-enkephalin (Met-ENK)-like IR was remarkably reduced at 0.5 h following nicotine administration and recovered to control levels by 2 h after nicotine (3 mg/kg, s.c.) administration. These results suggest that nicotine has an antinociceptive effect by promoting the release of Met-ENK, but not dynorphins and endorphins, from activated opioidergic neurons in spinal cord.
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.
Norikazu
N
Kiguchi
Takehiko
T
Maeda
Mie
M
Tsuruga
Akihiro
A
Yamamoto
Chizuko
C
Yamamoto
Masanobu
M
Ozaki
Shiroh
S
Kishioka
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004399:Dynorphins / Q000235:genetics; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; C036448:pre-prodynorphin; D009270:Naloxone; D004744:Enkephalin, Methionine; D011333:Pro-Opiomelanocortin; D008464:Mecamylamine; D009538:Nicotine; D004399:Dynorphins; C033660:preproenkephalin