Role of μ-opioid and NMDA receptors in the development and maintenance of repeated swim stress-induced thermal hyperalgesia

University of North Carolina at Chapel Hill, North Carolina, United States
Behavioural Brain Research (Impact Factor: 3.03). 03/2006; 167(2):205-11. DOI: 10.1016/j.bbr.2005.09.006
Source: PubMed


Repeated exposure to swimming stress induces a long-lasting hyperalgesia in the rat by mechanisms to be elucidated. Since opioid and glutamate neurotransmitter systems modulate pain, we now evaluated the effect of pharmacological blockade of opioid and glutamate receptors subtypes on forced swimming stress-induced hyperalgesia. Male rats were daily subjected to 10-20 min of forced or sham swimming for 3 days and thermal nociception was estimated twice, before each behavioral conditioning and 24 h after the last, using hot plate test. Selective opioid and NMDA receptor antagonists were administered i.p. either before each conditioning session or before the second nociception assessment. Unlike sham swimming rats, forced swimming rats showed significant reductions in hot plate response latencies (hyperalgesia) after the last swimming session, as compared to pre-stress values. Rats treated with the opioid receptor antagonists naloxone (0.1 mg/kg, non-subtype-selective) and naloxonazine (5 mg/kg, mu(1)-subtype-selective), before each forced swimming, did not become hyperalgesic, whereas those treated before the second post-stress assessment of nociception developed hyperalgesia. Naltrindole (0.5 mg/kg, delta-subtype-selective) and nor-binaltorphimine (0.5mg/kg, kappa-subtype-selective) were inactive in both administration schedules. The efficacy of morphine (3-7.5 mg/kg) to produce analgesia in forced swimming rats was lower than in sham swimming rats. Rats treated with the NMDA antagonist ketamine (5 mg/kg) before the forced swimming or the second post-stress assessment of nociception did not have hyperalgesia. Thus, swim stress-induced hyperalgesia might be initiated by the repeated stimulation of mu-opioid and NMDA receptors but maintained only by the activity of NMDA receptors.

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Available from: Heberto Suarez-Roca
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    • "null mice but not in their wild-type littermates. Although hyperalgesia following either single or repeated stress has been reported previously and different neurotransmitter/neuropeptide systems have been implicated in this response (Imbe et al., 2006; Khasar et al., 2008; Quintero et al., 2000; Suarez-Roca et al., 2006; Vidal and Jacob, 1982), our results are novel and showing that beta-endorphin is important not only in mediating antinociception elicited by a short swim, but also in preventing the development of a delayed hyperalgesic response. The hyperalgesic response could have been due an imbalance between the nociceptive inhibitory and excitatory mechanisms following repeated hot plate measurements. "
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