Pain
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Cognitive factors such as catastrophic thoughts regarding pain, and conversely, one's acceptance of that pain, may affect emotional functioning among persons with chronic pain conditions. The aims of the present study were to examine the effects of both catastrophizing and acceptance on affective ratings of experimentally induced ischemic pain and also self-reports of depressive symptoms. Sixty-seven individuals with chronic back pain completed self-report measures of catastrophizing, acceptance, and depressive symptoms. ⋯ Acceptance did not show any significant associations, when catastrophizing was also in the model, with any form of ratings of the induced pain. Catastrophizing, but not acceptance, was also significantly associated with self-reported depressive symptoms when these two variables were both included in a regression model. Overall, results indicate negative thought patterns such as catastrophizing appear to be more closely related to outcomes of perceived pain severity and affect in persons with chronic pain exposed to an experimental laboratory pain stimulus than does more positive patterns as reflected in measures of acceptance.
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Tibia fracture followed by limb immobilization in rats evokes nociceptive and vascular changes resembling complex regional pain syndrome type I (CRPS I). Previously we observed that substance P (SP) and interleukin-1beta (IL-1beta) signaling contribute to chronic regional nociceptive sensitization in this model. It is known that inflammasome multi-protein complexes containing caspase-1 and NALP1 are involved in the activation of the IL-1beta family of pro-nociceptive cytokines expressed in skin and other tissues. ⋯ Using this model we observed that: (1) inflammasome components and products NALP1, caspase-1, IL-1beta and IL-18 were present in low levels in normal skin, but expression of all these was strongly up-regulated after fracture, (2) NALP1, caspase-1 and IL-1beta were co-expressed in keratinocytes, and the number of NALP1, caspase-1, and IL-1beta positive cells dramatically increased at 4 weeks post-fracture, (3) LY303870, an NK1 receptor antagonist, effectively blocked fracture-induced up-regulation of activated inflammasome components and cytokines, (4) IL-1beta and IL-18 intraplantar injection induced mechanical allodynia in normal rats, and (5) both a selective caspase-1 inhibitor and an IL-1 receptor antagonist attenuated fracture-induced hindpaw mechanical allodynia. Collectively, these data suggest that NALP1 containing inflammasomes activated by NK1 receptors are expressed in keratinocytes and contribute to post-traumatic regional nociceptive sensitization. These findings highlight the possible importance of neuro-cutaneous signaling and innate immunity mechanisms in the development of CRPS.
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Previous research has demonstrated that the nociceptive flexion reflex (NFR) and pain-related evoked potentials are reduced in amplitude when elicited during the middle of the cardiac cycle. Despite these findings, suggesting a baroreceptor mechanism of antinociception during systole, pain intensity ratings reported in these studies were not modulated across the cardiac cycle. This discrepancy between the neurophysiological correlates of pain and its subjective experience was the focus of the current study that used a mixed block design to assess the effects of natural arterial baroreceptor activity on both the NFR and pain intensity and unpleasantness reports. ⋯ Finally, nociceptive responses did not differ among the R-wave to stimulation intervals for both painful and non-painful intensities. The observed phasic modulation of pain may be explained by a central nervous system alarm/defence reaction triggered by the unpredictability of the potentially damaging stimulation. The absence of systolic attenuation of nociceptive responding is compatible with previous evidence that baroreceptor modulation of the NFR is abolished under conditions of heightened arousal.
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Trigeminal neuralgia (TN) is a rare neuropathic facial pain disorder. Two forms of TN, classical TN (CTN) and atypical TN (ATN), are reported and probably have different aetiologies. The aim of the present study was to evaluate the functional integrity of the diffuse noxious inhibitory controls (DNIC) in (1) a group of patients with classical trigeminal neuralgia (CTN), (2) a group of patients with atypical trigeminal neuralgia (ATN), and (3) a group of healthy controls in order to determine if a descending pain modulation deficit could participate in the pathophysiology of TN pain. ⋯ Healthy participants and CTN patients showed a 21% and 16% reduction in thermode-induced pain following the immersion, respectively (all p-values <.01), whereas ATN patients experienced no change (p=.57). ATN patients also had more tender points (mechanical pain thresholds<4.0kg) than CTN and healthy controls (all p-values <.05). Taken together, these results suggest that the underlying physiopathology differs between CTN and ATN and that a deficit in descending inhibition may further contribute to the pain experienced by patients with ATN.
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Olesoxime is a small cholesterol-like molecule that was discovered in a screening program aimed at finding treatment for amyotrophic lateral sclerosis and other diseases where motor neurons degenerate. In addition to its neuroprotective and pro-regenerative effects on motor neurons in vitro and in vivo, it has been shown to have analgesic effects in rat models of painful peripheral neuropathy due to vincristine and diabetes. We used a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel, to determine whether olesoxime could reverse established neuropathic pain. ⋯ Giving olesoxime during the exposure to paclitaxel significantly and permanently reduced the severity of mechano-allodynia and mechano-hyperalgesia and significantly reduced the amount of sensory terminal arbor degeneration. Olesoxime targets mitochondrial proteins and its effects are consistent with the mitotoxicity hypothesis for paclitaxel-evoked painful peripheral neuropathy. We conclude that olesoxime may be useful clinically for both the prevention and treatment of paclitaxel-evoked painful peripheral neuropathy.