Pain
-
Randomized Controlled Trial Clinical Trial
Opposite effects of opioid blockade on the blood pressure-pain relationship in depressed and non-depressed participants.
The effect of the opioid antagonist naltrexone on the relationship between blood pressure and pain was examined in 24 participants with major depressive disorder and 31 non-depressed controls, before and after 25 min of stressful mental arithmetic. Pain was induced by immersing the non-dominant foot in 2 degrees C ice-water for as long as possible or until 4 min had elapsed (the cold pressor test). Blood pressure was measured before each cold pressor test, and at 2-min intervals during mental arithmetic. ⋯ However, naltrexone unmasked an association between blood pressure and pain--those with highest blood pressure reported least cold-induced pain. Thus, endogenous opioids apparently masked an analgesic mechanism linking elevated blood pressure with reduced sensitivity to pain in participants with major depressive disorder. Noradrenergic mechanisms involved in active coping, stress-induced analgesia and baroreflexes might account for these findings.
-
Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. ⋯ Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.
-
Evidence that patients with chronic pain selectively attend to pain-related stimuli presented in modified Stroop and dot-probe paradigms is mixed. The pain-related stimuli used in these studies have been primarily verbal in nature (i.e., words depicting themes of pain). The purpose of the present study was to determine whether patients with chronic pain, relative to healthy controls, show selective attention for pictures depicting painful faces. ⋯ The results of these analyses revealed that while chronic pain patients with high and low levels of fear both shifted attention away from happy faces, those with low fear shifted attention away from painful faces, whereas those with high fear shifted attention towards painful faces. These results suggest that patients with chronic pain selectively attend to facial expressions of pain and, importantly, that the tendency to shift attention towards such stimuli is positively influenced by high fear of pain/(re)injury. Implications of the findings and future research directions are discussed.
-
The present study was carried out to examine global gene expression in the brainstem, in a mouse facial carrageenan injection model of orofacial pain. Mice that received facial carrageenan injection showed increased mechanical allodynia, demonstrated by increased responses to von Frey hair stimulation of the face. The brainstem was harvested at 3 days post-injection, corresponding to the time of peak responses, and analyzed by Affymetrix Mouse Genome 430 2.0 microarrays. ⋯ Intraperitoneal injection of the P-selectin inhibitor KF38789 significantly reduced mechanical allodynia in the facial carrageenan-injected mice. P-selectin mediates the capturing of leukocytes from the bloodstream and rolling of leukocytes along the endothelial surface. We hypothesize that increased nociceptive input to the brainstem could attract circulating macrophages into the brain, resulting in neuroinflammation and pain.
-
We have developed a model in which inflammation contiguous to and within a dorsal root ganglion (DRG) was generated by local application of complete Freund's adjuvant (CFA) to the L4 lumbar spinal nerve as it exits from the intervertebral foramen. The periganglionic inflammation (PGI) elicited a marked reduction in withdrawal threshold to mechanical stimuli and an increase in heat pain sensitivity in the ipsilateral hindpaw in the absence of any hindpaw inflammation. The pain sensitivity appeared within hours and lasted for a week. ⋯ We also show that IL-1beta induces COX-2 expression and prostaglandin release in DRG neurons in vitro in a MAP kinase-dependent fashion. The COX-2 induction was prevented by ERK and p38 inhibitors. We conclude that periganglionic inflammation increases cytokine levels, including IL-1beta, leading to the transcription of COX-2 and prostaglandin production in the affected DRG, and thereby to the development of a dermatomally distributed pain hypersensitivity.