Pain
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We evaluated the effect of low doses of systemically administered tetrodotoxin (TTX) on the development and expression of neuropathic pain induced by paclitaxel in mice. Treatment with paclitaxel (2mg/kg, i.p., once daily during 5 days) produced long-lasting (2-4 weeks) heat hyperalgesia (plantar test), mechanical allodynia (electronic Von Frey test) and cold allodynia (acetone drop method), with maximum effects observed on days 7, 10 and 10-14, respectively. Acute subcutaneous treatment with 1 or 3 microg/kg of TTX reduced the expression of mechanical allodynia, whereas higher doses (3 or 6 microg/kg) were required to reduce the expression of cold allodynia and heat hyperalgesia. ⋯ Coadministration of a lower dose of TTX (3 microg/kg) also prevented the development of mechanical allodynia. No signs of TTX-induced toxicity or motor incoordination were observed. These data suggest that low doses of TTX can be useful to prevent and treat paclitaxel-induced neuropathic pain, and that TTX-sensitive subtypes of sodium channels play a role in the pathogenesis of chemotherapy-induced neuropathic pain.
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Significant decreases in the protein levels of potassium-chloride co-transporter 2 (KCC2) were detected in the ipsilateral spinal dorsal horn 4h following loose ligation of the sciatic nerve. These decreases were associated with a change in hindlimb weight distribution suggestive of pain behavior. In contrast, no changes in GABA-A receptor subunit alpha-1 levels were detected. ⋯ These data suggested that TrkB-dependent reduction in KCC2 protein levels in the spinal dorsal horn was an early consequence of peripheral nerve injury. This decrease in KCC2 may have elicited an early increase in overall dorsal horn neuronal excitability perhaps through a loss of GABA inhibition which is critically dependent on KCC2 activity. The increased neuronal excitability may in turn have caused enhanced and exaggerated communication between primary afferents and dorsal horn neurons to contribute to the early behavioral signs of pain.
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Given the high prevalence of depression in individuals with chronic pain and the negative outcomes associated with such comorbidity, the importance of assessing depressive symptoms is widely acknowledged by chronic pain specialists. The BDI-II is a commonly employed measure of depressive symptomatology at pain centres; however, little is known about its psychometric properties in this population. This study evaluated factorial validity, internal consistency, and gender invariance of the BDI-II in 481 patients with chronic pain. ⋯ Overall, results support the construct validity and internal consistency of the BDI-II for assessing depressive symptoms in both women and men with chronic pain. Results support the appropriateness of computing a total score and/or subscale scores. These results impact chronic pain researchers and clinicians, particularly given current trends toward empirically supported assessment.
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Tibia fracture in rats initiates a cascade of nociceptive, vascular, and bone changes resembling complex regional pain syndrome type I (CRPS I). Previous studies suggest that the pathogenesis of these changes is attributable to an exaggerated regional inflammatory response to injury. We postulated that the pro-inflammatory cytokine tumor necrosis factor alpha (TNF) might mediate the development of CRPS-like changes after fracture. ⋯ After fracture the rats developed hindpaw mechanical allodynia and unweighting, which were reversed by sTNF-R1 treatment. Consistent with the behavioral data, spinal Fos increased after fracture and this effect was inhibited by sTNF-R1 treatment. Collectively, these data suggest that facilitated TNF signaling in the hindlimb is an important mediator of chronic regional nociceptive sensitization after fracture, but does not contribute to the hindlimb warmth, edema, and bone loss observed in this CRPS I model.
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The purpose of this study was to verify the usefulness of an adaptation of the stress process model in organizing the psychological variables associated with the development of low-back-pain related disability. French-speaking Canadian workers on compensated sick leave (N=439) due to recent occupational low back pain (LBP) were evaluated during the sub-acute stage of LBP (between 30 and 83 days after injury). They were assessed for the following factors: life events, injury-specific cognitive appraisal, emotional distress, avoidance coping, and functional disability. ⋯ The stress model tested here reaffirms the importance of life events in the development of disability through the more established emotional distress factor. Also, cognitive appraisal appears to have an indirect effect on disability through activity avoidance and distress. This adaptation of the stress model makes it possible to integrate risk factors into a reduced set of meaningful factors and proposes a more general adaptation explanation of disability than the specific fear-avoidance model.