Involvement of medullary opioid-peptidergic and spinal noradrenergic systems in the regulation of formalin-induced persistent pain.
To confirm that endogenous opioid-peptidergic systems and monoaminergic systems participate in the regulation of pain, the effects of a narcotic antagonist naloxone, inhibitors of enkephalin-degrading enzymes and monoaminergic blockers on persistent pain induced by formalin were investigated. Rats were given formalin into the plantar region of the left hind-paw and the duration of licking responses was measured at periods of 0-10 min (period I), 10-30 min (period II), 30-60 min (period III) and 60-120 min (period IV). Naloxone was administered systemically through mini-osmotic pumps and there was an enhanced licking response at period III and a tendency toward enhancement at period IV. The duration of the licking response at period III was increased when naloxone was given into the fourth ventricle in a dose of 30 nmol/rat, but not when it was injected into the lumbo-sacral subarachnoid space in doses of 30 and 300 nmol/rat. Thiorphan and bestatin injected simultaneously into the fourth ventricle (50 micrograms/rat) depressed the licking response at period III. Intrathecal injection of phentolamine significantly enhanced the licking response at periods I-III and produced a similar, but weaker effect at period IV. Intrathecal injection of propranolol and methysergide did not affect the response. These results suggest that opioid-peptidergic systems in the brain stem and noradrenergic systems in the spinal cord (via alpha-adrenoceptors) participate in the regulation of pain.
Sugimoto
M
M
Kuraishi
Y
Y
Satoh
M
M
Takagi
H
H
D000818:Animals; D004723:Endorphins / Q000502:physiology*; D005557:Formaldehyde / Q000494:pharmacology; D007278:Injections, Spinal; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology*; D015244:Thiorphan; D013997:Time Factors; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology
D004723:Endorphins; D005557:Formaldehyde; D009270:Naloxone; D015244:Thiorphan; D008625:Tiopronin; D007930:Leucine; C012211:ubenimex; D009638:Norepinephrine