Classical conditioning of front paw and hind paw footshock induced analgesia (FSIA): naloxone reversibility and descending pathways

Brain Res. 1982 Jul 8;243(1):119-32. doi: 10.1016/0006-8993(82)91125-8.


Opiate and non-opiate footshock induced analgesia (FSIA) has recently been observed to be differentially elicited dependent upon the body region shocked; front paw and hind paw shock produce opiate and non-opiate analgesia, respectively. Previous studies have shown that footshock can also produce classically conditioned analgesia; that is, when shock is delivered to an animal, environmental cues become associated with the noxious stimulus such that these cues become capable, in and of themselves, of producing potent analgesia. The present series of experiments examined analgesia classically conditioned to either front paw or hind paw shock. The non-electrified shock grid served as the conditioned stimulus (CS), 90-s footshock as the unconditioned stimulus (UCS) and tail-flick inhibition as the unconditioned response (UCR). Following CS-UCS pairings, exposure to the non-electrified grid reliably produced prolonged analgesia. This classically conditioned analgesia appears to involve endogenous opioids, regardless of the body region shocked during conditioning trials, since the analgesia is attenuated by systemic naloxone and shows cross-tolerance to morphine. A spinal opioid site is involved since 1 microgram of naloxone delivered directly to the lumbosacral cord antagonizes the analgesia. Like front paw (opiate) FSIA, CCA can be prevented but cannot be reversed by naloxone; naloxone can antagonize classically conditioned analgesia only if it is delivered prior to exposure to the conditioned stimulus. Lastly, a similarity was recognized between classically conditioned analgesia and the analgesia induced by morphine, brain stimulation, front paw shock and hind paw shock in that all are mediated via descending pathways within the dorsolateral funiculus of the spinal cord.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesia
  • Animals
  • Conditioning, Classical* / drug effects
  • Drug Tolerance
  • Electroshock
  • Forelimb
  • Hindlimb
  • Male
  • Morphine / pharmacology
  • Naloxone / pharmacology*
  • Rats
  • Rats, Inbred Strains


  • Naloxone
  • Morphine