Pain
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Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary evidence suggests reduced experimental pain sensitivity in this disorder. The questions addressed in the present study were whether pain perception would also be reduced in PTSD patients who are not suffering from chronic pain symptoms, and whether a reduction in pain sensitivity would also be present in combat veterans who did not develop PTSD. For this, we determined thermal detection and pain thresholds in 10 male combat-related PTSD patients, 10 combat control subjects (no PTSD) and 10 healthy controls without combat experience. ⋯ However, these stimuli could not distinguish between the two groups due to ceiling effects. When using longer-lasting heat stimulation at different temperatures (30s duration; method of fixed stimuli), we found significantly lower frequency of pain reports in PTSD patients compared with both combat and healthy controls, as well as significantly lower pain ratings. Our results suggest an association of PTSD with reduced pain sensitivity, which could be related to PTSD-related (neuro-)psychological alterations or to a pre-existing risk factor for the disorder.
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Although N-methyl-d-aspartate (NMDA) receptor antagonists potentiate antinociceptive effects induced by various exogenous opioids at the spinal, supraspinal, or peripheral level, less is known regarding the interaction between NMDA and endogenous opioids in antinociception. We therefore assessed the effects of NMDA receptor antagonists on endogenous opioids in antinociception at the peripheral level by testing the ability of the locally administered receptor antagonists to modify pain-related behavior induced by carrageenan injection into the knee joint. The NMDA receptor antagonist AP-5 or the exogenous opioid morphine was injected intra-articularly before carrageenan injection and 5h after carrageenan injection, respectively. ⋯ Intriguingly, injection of naloxone 5h after carrageenan injection reversed the antinociceptive effects of AP-5 pre-treatment, although naloxone alone had no effect on carrageenan-induced pain-related behavior. Western blots showed that AP-5 pre-treatment followed by carrageenan injection resulted in a higher level of beta-endorphin protein in the DRG and saphenous nerve, but not in the synovial membrane, than that observed following saline control treatment. These results suggest that inhibition of the NMDA receptor unmasks antinociception induced by endogenous opioids at the peripheral level, partly through the increased protein level of the endogenous mu-opioid peptide beta-endorphin in DRG and saphenous nerve.
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The current study assessed whether the chronic constriction injury (CCI) model of neuropathic pain causes depression-like behaviour in animals, and if this depression-like behaviour can be reversed by anti-nociceptive and/or antidepressant drugs. CCI of the sciatic nerve in rats was selected as a neuropathic pain model, mechanical hypersensitivity was assessed by punctuate mechanical stimuli, and depression-like behaviour was evaluated in the forced swimming test (FST) measuring the time of immobility, climbing and swimming. The CCI rats displayed a significant mechanical hypersensitivity (sham 27+/-2g, CCI 12+/-2g; P<0.001) and a significant increase in time of immobility (sham 133+/-14s, CCI 201+/-9s; P<0.001). ⋯ In contrast in CCI animals the cannabinoid CB2-selective agonist GW405833 (2,3-dichloro-phenyl)-[5-methoxy-2-methyl-3-(2-morpholin-4-yl-ethyl)-indol-1-yl]-methanone) (30 mg/kg) significantly attenuated immobility (CCI+vehicle 191+/-7s, GW405833 145+/-14s; P<0.01) and mechanical hypersensitivity (CCI+vehicle 15+/-1g, CCI+GW405833 24+/-1g; P<0.001). Moreover, differently from desipramine, GW405833 did not change the climbing behaviour. These data suggest that rats subjected to the CCI model of neuropathic pain develop depression-like behaviour, which can be reversed by appropriate anti-nociceptive treatment.