Richard A. Hughes

Exposure to a nonfunctional hot plate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats

Rats not exposed to a hot plate with or without morphine and later tested on the functional hot plate with or without morphine, displayed increased paw lick latency relative to same-injected rats given pretest hot plate exposure. This analgesic effect, was termed behavioral analgesia since it, unlike morphine-induced analgesia, was not reversed by naloxone (Experiment 2). Behavioral tolerance was evident in animals exposed to the nonfunctional hot plate regardless of drug treatment and was dissociated from pharmacological tolerance. Behavioral analgesia and tolerance reported here may involve habituation to novel distractive stimuli associated with the hot plate test environment.

Shock-elicited flight response in chickens as an index of morphine analgesia

Morphine influence on a flight response elicited by wing shock was examined in 17-day-old chickens. The chickens received either morphine (30 mg/kg) or saline on two days and were tested for responsivity to wing shock 30 min after each injection. On a third day all chickens received saline injections and were tested again. Tests consisted of delivering wing shock at increasing intensity to determine the threshold of a species-typical flight response. Morphine significantly increased the flight response th reshold on the first test (analgesia), but not on the second test. Shock intensity values required to elicit the flight response in morphine and saline groups did not differ significantly on the third test when all birds received saline. In contrast to previous evidence, these results demonstrate morphine analgesia in chickens using a dose that approximates the analgesic dose range reported for other species.

Strain-dependent morphine-induced analgesic and hyperalgesic effects on thermal nociception in domestic fowl (Gallus gallus)

The effects of morphine (30 mg/kg), naloxone (5 mg/kg), and morphine with naloxone on distress vocalizations and thermal nociception were examined in different strains of domestic fowl. Naloxone by itself did not significantly affect vocalizations or thermal nociception. Morphine produced a naloxone-reversible attenuation of vocalizations that was not strain dependent. Morphine produced a strain-dependent analgesic (Rhode Island Red strain) and hyperalgesic (White Leghorn and Cal-White strains) effect on tests of thermal nociception. Both the analgesic and hyperalgesic effects were reversed by naloxone. These opposite effects on thermal nociception may reflect the effects of selective breeding on opioid receptor subtype.

Naloxone interactions with morphine- and shock-potentiated tonic immobility in chickens

Opiate receptor involvement in tonic immobility was examined by administering various does of the opiate antagonist naloxone before measuring morphine-potentiated, shock-poteniated or unpotentiated tonic immobility in chickens. Naloxone attenuated morphine-potentiated, but not shock-potentiated or unpotentiated tonic immobility. Morphine-potentiated tonic immobility appears to be opiate specific.

Differential effects of handling on isolation-induced vocalizations, hypoalgesia, and hyperthermia in domestic fowl

The effects of handling and subsequent brief isolation on vocalizations, thermal nociception, and thermoregulation were examined in 7-day-old cockerels. In Experiment 1, fifteen min of isolation elicited more vocalizations in handled than nonhandled chicks. Nonhandled chicks exhibited longer response latencies than handled chicks. In general, isolated chicks exhibited longer jump response latencies (i.e., hypoalgesia) on hot-plate tests than chicks tested immediately upon removal from the brooder. Compared to handled chicks tested immediately, all other groups exhibited increased core body temperatures. Experiment 2 examined these handling and isolation effects after 15 min of isolation with or without conspecifics. Chicks isolated alone vocalized more than chicks isolated with conspecifics. As in Experiment 1, handled chicks vocalized more than nonhandled chicks. Nonhandled chicks exhibited longer response latencies than handled chicks on hot-plate tests. Isolation-induced hypoalgesia was observed only in handled chicks that were isolated without conspecifics. Core body temperatures were highest in chicks isolates without conspecifics. Additionally, chicks isolated with conspecifics exhibited higher core body temperature than chicks tested immediately. Decreased core body temperature due to handling exposure was observed only in chicks tested immediately. These results demonstrate that isolation effects on vocalizations and nociception are primarily due to social isolation and that isolation effects on thermoregulation are a result of both social and environmental factors. Moreover, the increase in isolation-induced vocalizations in handled animals does not correlate well with the decrease in isolation-induced hypoalgesia and hyperthermia displayed by handled animals.

Dose and temporal parameters of morphine-induced hyperalgesia in domestic fowl

Recent research in this laboratory has identified a biological model in which morphine produced a hyperalgesic response to a noxious thermal stimulus. Morphine effects, however, were examined at only one injection-to-test interval (10 min). Because a single injection-to-test interval is relatively uninformative, the present research was designed to more fully characterize this morphine hyperalgesic effect. In Experiment 1, 15-day-old White Leghorn cockerels were placed on a hot plate (59 degrees C) in 10 min after injection of morphine (1.25, 2.5, 5.0, 10.0 mg/ml/kg) or the distilled water vehicle (1 ml/kg). Latency to perform a jump response or attainment of a 90-sec no-jump criterion were recorded. Experiment 2 examined morphine effects (2.5 mg/ml/kg) on hot plate jump latencies at various injection-to-test intervals (10, 30, 60, and 240 min). Morphine produced a dose-dependent hyperalgesic response. Temporal characteristics of morphine effects were evident as a U-shaped function. The dose and temporal characteristics of morphine-induced hyperalgesia in White Leghorn cockerels are similar to the dose and temporal characteristics of morphine-induced analgesia typically seen in other species.

Opiate effects of isolation stress in domestic fowl

In an attempt to examine the role of opioid system functioning in social attachment and isolation stress in young domestic fowl, the effects of morphine (5.0 mg/kg) and naloxone (5.0 mg/kg) were evaluated on distress vocalizations, thermal nociception, thermoregulation, and respiration following 15 min of isolation in 7-day-old White-Leghorn cockerels. Morphine decreased and naloxone increased distress vocalizations in isolated chicks. Isolation produced an increase in jump response latencies (i.e., hypoalgesia) on a standard hot-plate test. In general, morphine decreased and naloxone increased mean jump latencies in both isolated and nonisolated chicks. Isolation produced an increase in core body temperature (i.e., hyperthermia); morphine decreased and naloxone increased core body temperatures independent of the isolation manipulation. Social isolation did not affect respiration. However, morphine depressed respiration in both isolated and nonisolated chicks. These results support the notion that opioid systems modulate social attachment and isolation stress.

Morphine hyperalgesic effects on the formalin test in domestic fowl (Gallus gallus)

Preliminary research demonstrated that formalin injected into the foot of leghorn cockerels elicited significantly more footlifts of longer duration than physiological saline. The formalin test was subsequently used to examine morphine effects in this species. Previous research demonstrated strain-dependent naloxone-reversible morphine hyperalgesia against thermal nociception in cockerels. In Experiment 1 herein White Leghorn cockerels were given either 0.0, 0.5, 1.5, or 2.5% formalin SC into the foot 30 min after an IM injection of either physiological saline or 2.5 mg/kg morphine sulfate. The frequency and duration of formalin-elicited footlifts increased significantly as a function of formalin concentration. Morphine significantly increased footlift frequency and duration at all but the 0.0% formalin concentration. Morphine inhibited respiration in these animals. In Experiment 2, naloxone (5.0 mg/kg) significantly reversed both the hyperalgesia and the respiratory depression induced by morphine. These results demonstrate that morphine hyperalgesia in leghorn cockerels is neither unique to hot plate test procedures nor peculiar to thermal nociception. Atypical morphine effects in this model may be specific to nociception, however, because hyperalgesia was not accompanied by atypical morphine effects on respiration.

Effects of selective opiate antagonists on morphine-induced hyperalgesia in domestic fowl

Although morphine typically produces analgesia in a variety of species, recent research has identified a biological model in which morphine produces a naloxone-reversible, paradoxical hyperalgesic response to a noxious thermal stimulus in young domestic fowl. The present study examined opioid receptor-mediation of this atypical opiate effect. Patterns of morphine hyperalgesia (1.25 to 5.0 mg/kg IM) were examined on a standard hot-plate test following administration (10 micrograms/5 microliters ICV) of the mu antagonist beta-funaltrexamine, the delta antagonist naltrindole, or the kappa antagonist nor-binaltorphimine in 15-day-old White Leghorn cockerels. Respiration measures were also recorded because they are indicative of opiate effects. Morphine produced a dose-dependent decrease in mean jump latencies (i.e., hyperalgesic effect). Mu receptor antagonism attenuated this morphine-induced hyperalgesic effect. Kappa receptor antagonism attenuated morphine-induced hyperalgesia only at the highest morphine dose (i.e., 5.0 mg/kg) and delta receptor antagonism failed to attenuate morphine-induced hyperalgesia. These results suggest that morphine-induced hyperalgesia, like morphine-induced analgesia, is mediated primarily by mu receptor activation.

Codeine analgesic and morphine hyperalgesic effects on thermal nociception in domestic fowl

The effects of codeine phosphate and morphine sulfate (2.5, 15.0, and 30 mg/ml/kg; IM) on latency of a jump response elicited by a noxious (61 degrees C) thermal stimulus were studied in White Leghorn cockerels at 15-16 days posthatch. Codeine induced a significant dose-dependent increase in jump response latency (analgesic effect), whereas morphine at each dose induced a significant decrease in jump response latency (hyperalgesic effect). Naloxone (5 mg/ml/kg) reversed the hyperalgesic effect of morphine (30 mg/ml/kg) and potentiated codeine analgesic effects. It is unlikely that codeine analgesic effects in domestic fowl reflect demethylation of codeine to morphine. These opposite codeine and morphine effects may reflect the interaction of these opiates at different populations of opioid receptors or at different substrates.