Opioid-induced hypernociception is associated with hyperexcitability and altered tetrodotoxin-resistant Na+ channel function of dorsal root ganglia.

ABSTRACT: Opiates are potent analgesics for moderate to severe pain. Paradoxically, patients under chronic opiates have reported hypernociception, the mechanisms of which are unknown. Using standard patch-clamp technique, we examined the excitability, biophysical properties of tetrodotoxin-resistant (TTX-R) Na(+) and transient receptor potential vanilloid 1 (TRPV1) channels of dorsal root ganglia neurons (DRG) (L(5)-S(1)) from mice pelleted with morphine (75 mg) or placebo (7 days). Hypernociception was confirmed by acetic acid-writhing test following 7-day morphine. Chronic morphine enhanced the neuronal excitability, since the rheobase for action potential (AP) firing was significantly (P < 0.01) lower (38 ± 7 vs. 100 ± 15 pA) while the number of APs at 2× rheobase was higher (4.4 ± 0.8 vs. 2 ± 0.

SUBMITTER: Ross GR 

PROVIDER: S-EPMC3330728 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature