Medial forebrain stimulation enhances intracranial nociception and attenuates morphine analgesia suggesting the existence of an endogenous opioid antagonist.
The purpose of this experiment was to test in the rat the hypotheses that activation of the brain reward system would attenuate the effects of intracranial nociceptive stimulation and would potentiate the antinociceptive effects of morphine. In this experiment pain (nociception) was generated by electrical stimulation of a brain pain pathway, the mesencephalic reticular formation (MRF) of the rat. Reward pathway stimulation was to the medial forebrain bundle at the level of the lateral hypothalamus (MFB-LH). Current thresholds for escape from MRF stimulation were determined using a modification of the psychophysical methods of limits. MRF stimulation was delivered concurrently with different intensities of non-contingent MFB-LH stimulation. The effects of morphine and saline were determined under all stimulation conditions. Contrary to expectation MFB-LH stimulation significantly lowered MRF stimulation escape thresholds. Morphine administration elevated MRF thresholds in the absence of MFB-LH stimulation. However, this effect was blocked by concurrent MFB-LH stimulation. These findings, which mimic the effects of the opiate antagonist naloxone, i.e., potentiating of pain and antagonism of morphine's analgesic effects, suggest the presence of an endogenous opiate receptor antagonist.
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, United States. ckornets@bu.edu
Conan
C
Kornetsky
Clifford M
CM
Knapp
Lisa
L
Tozier
Arlene
A
Pak
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D018847:Opioid Peptides / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D016548:Prosencephalon / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009020:Morphine