lithium-chloride and Disease

The data reported in this experiment provide the first systematic exploration of the effectiveness of an odor previously paired with an aversive reinforcer other than shock on eliciting various behavioral expressions of fear in the rat. Specifically, we measured potentiation of the acoustic startle response, freezing, and analgesia in the presence of an odor previously paired with an illness-inducing agent (lithium chloride; LiCl). We found that this odor elicited freezing and analgesia, but failed to potentiate the startle response. The results are discussed in terms of (1). potential threshold differences for various expressions of learned fear and (2). the possibility that the content of the learning established by odor-shock pairings differ from those established by odor-illness pairings.

Topics: Analgesia; Animals; Avoidance Learning; Conditioning, Classical; Disease; Fear; Immobilization; Lithium Chloride; Male; Odorants; Rats; Rats, Sprague-Dawley; Reflex, Startle

Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. Rev. 23 (1999) 1059]. Thus, we examined whether LiCl, LPS or cues paired with LiCl could reduce morphine analgesia. Morphine analgesia in the tail flick test was reduced 24 h but not 7 days following injection with LiCl, and 24 h following injection with LPS. In addition, morphine analgesia was reduced in the hot plate test 40 min and 24 h following LiCl. Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.

Topics: Acute Disease; Analgesia; Analgesics, Opioid; Animals; Conditioning, Psychological; Cues; Disease; Hyperalgesia; Lipopolysaccharides; Lithium Chloride; Male; Morphine; Neuroimmunomodulation; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Wistar

It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors.

Topics: Animals; Avoidance Learning; Disease; Formaldehyde; Hot Temperature; Hyperalgesia; Injections, Intraperitoneal; Lipopolysaccharides; Lithium Chloride; Male; Nociceptors; Pain Measurement; Rats; Rats, Sprague-Dawley; Reaction Time; Skin Temperature; Taste

After a drug conditioned stimulus (CS) has been injected prior to lithium chloride as the unconditioned stimulus (US) on five occasions, the drug CS becomes able to evoke a conditioned antisickness response (CAR). This CAR is implied by the finding that the CS drug mitigates the conditioned saccharin aversion produced by lithium when it is administered in the interval between saccharin consumption and lithium injection. The following drugs were tested and are listed in approximate order of their effectiveness in producing a conditioned antisickness effect: pentobarbital, ethanol, morphine, amphetamine, and chlordiazepoxide.

Topics: Animals; Avoidance Learning; Chlorides; Conditioning, Classical; Cues; Disease; Lithium; Lithium Chloride; Male; Psychotropic Drugs; Rats; Rats, Inbred Strains; Saccharin; Taste