Low-dose intrathecal morphine facilitates the spinal flexor reflex by releasing different neuropeptides in rats with intact and sectioned peripheral nerves.
The facilitatory effect of intrathecal (i.t.) morphine on the excitability of the nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats with intact or sectioned sciatic nerves. Low doses of i.t. morphine (10 ng in rats with intact nerves and 10 or 100 ng in rats with sectioned nerves) facilitated the flexor reflex. Higher doses of morphine caused facilitation followed by reflex depression. Facilitation of the flexor reflex induced by 10 or 100 ng morphine was prevented by i.t. naloxone (1 microgram). In rats with intact sciatic nerves the facilitation was partially antagonized by the tachykinin antagonist spantide II (D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nle 11)-substance P (SP), indicating that the reflex facilitation evoked by low doses of morphine may be due to the release of SP and perhaps other neuropeptides. In axotomized animals, 14-20 days after unilateral sciatic nerve section, spantide II failed to antagonize morphine-induced facilitation, suggesting that SP or other tachykinins, no longer played a role in this effect. In contrast, the vasoactive intestinal peptide (VIP) antagonist (N-Ac-Tyr1,D-Phe2)-GRF (1-29)-NH2 blocked morphine-induced reflex facilitation in axotomized rats, but not in rats with intact nerves. The present study provides evidence that low doses of morphine may induce the release of excitatory neuropeptides, thereby facilitating spinal nociceptive transmission. The identity of the neuropeptides depends on whether or not peripheral axons are intact, tachykinins in rats with intact nerves and VIP in axotomized rats.
Wiesenfeld-Hallin
Z
Z
Karolinska Institute, Department of Clinical Physiology, Huddinge University Hospital, Sweden.
Xu
X J
XJ
Håkanson
R
R
Feng
D M
DM
Folkers
K
K
D000818:Animals; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D005260:Female; D007278:Injections, Spinal; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*
C065446:spantide II; D013373:Substance P; D009270:Naloxone; D014660:Vasoactive Intestinal Peptide; D009020:Morphine