Analgesic efficacy of buprenorphine in the presence of high levels of SDF-1α/CXCL12 in the brain.
Although morphine is often the best option for treating acute and chronic severe pain, its analgesic activity can be blocked in situations in which there are elevated levels of chemokines. Indeed, recently we have shown that elevated brain levels of the chemokine stromal cell-derived growth factor-1alpha (SDF-1α/CXCL12, the ligand of the HIV co-receptor CXCR4) diminish the antinociceptive effect of morphine. The purpose of the present study was to investigate whether such an effect is restricted to morphine or extends to other opioid medications such as buprenorphine. A sterilized stainless-steel C313G guide cannula was implanted into the periaqueductal grey (PAG), a brain region critical to the processing of pain signals, and a primary site of action of many analgesic compounds. The cold-water (-3°C) tail-flick test (CWT) was used to measure antinociception. Rats were pretreated with SDF-1α/CXCL12 administered into the PAG, and the antinociceptive actions of buprenorphine were measured. Direct infusion of SDF-1α/CXCL12 into the PAG failed to alter the antinociceptive action of buprenorphine. The presence of SDF-1α/CXCL12 in the PAG differentially alters the antinociceptive function of opioid medications. While it was able to diminish the antinociception induced by morphine (Adler et al., 2006), SDF-1α/CXCL12 did not affect the buprenorphine-induced antinociception. Buprenorphine appears to be more effective in the presence of high levels of SDF-1α/CXCL12 in the brain (which frequently occurs during neuroinflammatory conditions).
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. kbenamar@temple.edu
Khalid
K
Benamar
Jonathan
J
Palma
Alan
A
Cowan
Ellen B
EB
Geller
Martin W
MW
Adler
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002047:Buprenorphine / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D054377:Chemokine CXCL12; D002047:Buprenorphine