The journal of pain : official journal of the American Pain Society
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Looking at one's own body might induce visual analgesia. However, the cognitive and physiological mechanisms underlying such visual analgesia are unknown. Because body and pain representations in the brain are multisensory, and have been reported to partially overlap, we herein investigated whether experimentally-induced changes in bodily self-consciousness (BSC) modulate pain. We measured physiological responses to pain (skin conductance response [SCR]) and the subjective experience of pain, under conditions of manipulated BSC. First we investigated whether looking at a virtual body that was associated with BSC (embodiment) reduced responses to pain, which revealed the effect of BSC on pain processing. Second, we manipulated the visual size of the virtual body during painful stimulation, a procedure known to modulate pain processing when used with biological bodies, but never studied with embodied avatars. We found reduced SCR in conditions of illusory embodiment, and a negative correlation between virtual body size and SCR, whereas subjective pain ratings were not affected by these manipulations. These results suggest that pain processing is modulated during illusory states of BSC and that these changes are greater for larger virtual bodies, which sustains that pain and its physiological mechanisms are associated with the bodily self, opening promising avenues for future pain treatments. ⋯ We show that BSC affects the processing of painful stimuli with induction of different levels of pain responses for embodied virtual bodies of different sizes. Our data reveal novel links between pain and self and suggest that embodied virtual bodies are a promising technique for future pain treatments.
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Thiazolidinedione drugs (TZDs) such as pioglitazone are approved by the U.S. Food and Drug Administration for the treatment of insulin resistance in type 2 diabetes. However, whether TZDs reduce painful diabetic neuropathy (PDN) remains unknown. Therefore, we tested the hypothesis that chronic administration of pioglitazone would reduce PDN in Zucker Diabetic Fatty (ZDF(fa/fa) [ZDF]) rats. Compared with Zucker Lean (ZL(fa/+)) controls, ZDF rats developed: (1) increased blood glucose, hemoglobin A1c, methylglyoxal, and insulin levels; (2) mechanical and thermal hyperalgesia in the hind paw; (3) increased avoidance of noxious mechanical probes in a mechanical conflict avoidance behavioral assay, to our knowledge, the first report of a measure of affective-motivational pain-like behavior in ZDF rats; and (4) exaggerated lumbar dorsal horn immunohistochemical expression of pressure-evoked phosphorylated extracellular signal-regulated kinase. Seven weeks of pioglitazone (30 mg/kg/d in food) reduced blood glucose, hemoglobin A1c, hyperalgesia, and phosphorylated extracellular signal-regulated kinase expression in ZDF. To our knowledge, this is the first report to reveal hyperalgesia and spinal sensitization in the same ZDF animals, both evoked by a noxious mechanical stimulus that reflects pressure pain frequently associated with clinical PDN. Because pioglitazone provides the combined benefit of reducing hyperglycemia, hyperalgesia, and central sensitization, we suggest that TZDs represent an attractive pharmacotherapy in patients with type 2 diabetes-associated pain. ⋯ To our knowledge, this is the first preclinical report to show that: (1) ZDF rats exhibit hyperalgesia and affective-motivational pain concurrent with central sensitization; and (2) pioglitazone reduces hyperalgesia and spinal sensitization to noxious mechanical stimulation within the same subjects. Further studies are needed to determine the anti-PDN effect of TZDs in humans.
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Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. ⋯ Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain.
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Recent data show that dry eye (DE) susceptibility and other chronic pain syndromes (CPS) such as chronic widespread pain, irritable bowel syndrome, and pelvic pain, might share common heritable factors. Previously, we showed that DE patients described more severe symptoms and tended to report features of neuropathic ocular pain (NOP). We hypothesized that patients with a greater number of CPS would have a different DE phenotype compared with those with fewer CPS. We recruited a cohort of 154 DE patients from the Miami Veterans Affairs Hospital and defined high and low CPS groups using cluster analysis. In addition to worse nonocular pain complaints and higher post-traumatic stress disorder and depression scores (P < .01), we found that the high CPS group reported more severe neuropathic type DE symptoms compared with the low CPS group, including worse ocular pain assessed via 3 different pain scales (P < .05), with similar objective corneal DE signs. To our knowledge, this was the first study to show that DE patients who manifest a greater number of comorbid CPS reported more severe DE symptoms and features of NOP. These findings provided further evidence that NOP might represent a central pain disorder, and that shared mechanistic factors might underlie vulnerability to some forms of DE and other comorbid CPS. ⋯ DE patients reported more frequent CPS (high CPS group) and reported worse DE symptoms and ocular and nonocular pain scores. The high CPS group reported symptoms of NOP that share causal genetic factors with comorbid CPS. These results imply that an NOP evaluation and treatment should be considered for DE patients.
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Catastrophizing is associated with negative outcomes in chronic pain and illness. The communal coping model (CCM) and cognitive behavioral (CB) formulations provide differing accounts of the function of catastrophizing in these contexts. In the present study we examined predictions from CCM and CB theoretical models in a sample of 116 patients with chronic fatigue to test (1) whether patient-reported solicitous responses from significant others mediate the relationship of catastrophizing with patient-reported pain and fatigue behaviors, as predicted by the CCM; and (2) whether pain and fatigue behaviors mediate the relationship of catastrophizing with solicitous responses, consistent with a CB model. This work is a secondary data analysis in which the strength of the indirect (i.e., mediating) effects among study variables was examined. Consistent with CB models, pain and fatigue behaviors were associated with catastrophizing and solicitous responses, and there was a significant indirect effect of catastrophizing on solicitous responses through pain and fatigue behaviors. Results were inconsistent with the CCM; catastrophizing was not significantly associated with solicitous responses, nor did solicitous responses mediate the relationship between catastrophizing and pain or fatigue behaviors. These findings highlight the importance of behavioral expressions of pain and fatigue in understanding the relationship of catastrophizing to solicitous responses in chronic fatigue. ⋯ This study of chronic fatigue patients tested CB and CCMs of catastrophizing, pain, and fatigue behaviors, and solicitous responses by significant others. Results were more consistent with CB formulations, which highlighted the importance of behavioral expressions of pain and fatigue in understanding the relationship of catastrophizing to solicitous responses.