Pharmacological relationship between nicotinic and opioid systems in analgesia and corticosterone elevation.
OBJECTIVE
Although a pharmacological relationship is known to exist between nicotine and morphine, the exact mechanisms are unclear. Here, we investigated crosstalk between the endogenous opioid system and nicotinic acetylcholine receptors (nAChRs), specifically in nicotine-induced analgesia and activation of the hypothalamic-pituitary-adrenal (HPA) axis.


METHODS
Nicotine and morphine were administered subcutaneously to mice and the effects of these drugs on analgesia and serum corticosterone (SCS) levels were evaluated by the tail-pinch method and fluorometric assay, respectively.


RESULTS
Both nicotine and morphine produced analgesia and SCS increase after a single injection. Nicotine-induced analgesia was prevented by both mecamylamine (MEC; 1mg/kg) and naloxone (NLX; 1mg/kg), and also by repeated administration of morphine or nicotine. Morphine-induced analgesia was prevented by NLX, but not MEC, and by repeated administration of morphine, but not nicotine. Conversely, the nicotine-induced increase in SCS level was prevented by MEC, but not NLX. Morphine-induced SCS increase was prevented by NLX, but not MEC. Moreover, nicotine-induced analgesia was suppressed by dihydro-β-erythroidine (DHβE; an antagonist for the α4β2 nAChR) or methyllycaconitine (MLA; an antagonist for the α7 nAChR). The nicotine-induced increase in SCS level was suppressed by DHβE, but not MLA.


CONCLUSIONS
Nicotine-induced analgesia may involve the endogenous opioid system through crosstalk with nicotinic pathways. However, the relationship between these systems does not extend to cooperative actions in nicotine-induced HPA-axis activation.
Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Akihiro
A
Yamamoto
Norikazu
N
Kiguchi
Yuka
Y
Kobayashi
Takehiko
T
Maeda
Keiko
K
Ueno
Chizuko
C
Yamamoto
Shiroh
S
Kishioka
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005470:Fluorometry; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D020239:Receptor Cross-Talk
D000701:Analgesics, Opioid; D018722:Nicotinic Agonists; D009538:Nicotine; D009020:Morphine; D003345:Corticosterone