Pain
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Comparative Study
Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion?
Neuropathic pain can be caused by a variety of nerve lesions and it is unsettled whether it should be categorised into distinct clinical subtypes depending on aetiology or type of nerve lesion or individualised as a specific group, based on common symptomatology across aetiologies. In this study, we used a multivariate statistical method (multiple correspondence analyses) to investigate associations between neuropathic positive symptoms (assessed with a specific questionnaire, the Neuropathic Pain Symptom Inventory [NPSI]) and aetiologies, types of nerve lesion and pain localisations. We also examined the internal structure of the NPSI and its relevance to evaluation of symptoms of evoked pains by exploring their relationships with clinician-based quantified measures of allodynia and hyperalgesia. ⋯ Multiple correspondence analyses indicated few associations between symptoms (or dimensions) and aetiologies, types of lesions, or pain localisations. Exceptions included idiopathic trigeminal neuralgia and postherpetic neuralgia. We found that there are more similarities than differences in the neuropathic positive symptoms associated with a large variety of peripheral and central lesions, providing rationale for subgrouping aetiologically diverse neuropathic patients into a specific multidimensional category for therapeutic management.
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Comparative Study
Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation.
In this study, we recorded activity from afferent fibers innervating the mouse plantar skin, the same region evaluated in pain behavior experiments. We compared responses of afferents from incised and unincised hind paw skin. The plantar skin together with attached medial and lateral plantar nerves was dissected until they could be completely removed intact and placed in an organ bath chamber continuously perfused with oxygenated Kreb's solution with the temperature maintained at 32 degrees C. ⋯ Few fibers were excited by cooling. Heat sensitization of primary afferents was more prominent when activities of unclassified afferents are included. The preparation allows us to study afferent function of the same tissue that is examined for in vivo pain behavior assays in mice.
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Comparative Study
Endogenous kappa-opioid receptor systems inhibit hyperalgesia associated with localized peripheral inflammation.
Peripheral inflammation evokes functional and biochemical changes in the periphery and spinal cord which result in central sensitization and hypersensitivity. Inhibitory control systems from the rostral ventromedial medulla (RVM) are also activated. The present study investigates whether endogenous kappa-opioid receptor (KOPr) systems contribute to these neuroadaptations. ⋯ These data demonstrate a previously unrecognized role of endogenous KOPr systems in inhibiting hyperalgesia during inflammation. Furthermore, they demonstrate that decreased KOPr activity in either the spinal cord or RVM not only enhances mechanical and thermal hyperalgesia of the inflamed limb but also leads to an unmasking of mechanical hyperalgesia at a site remote from inflammation. The differential effects of KOPr antagonism on mechanical versus thermal thresholds for the non-inflamed paw support the notion that distinct neuroanatomical or neurochemical mechanisms modulate the processing of thermal versus mechanical stimuli.
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Randomized Controlled Trial Multicenter Study
Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.
Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. ⋯ Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.
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Randomized Controlled Trial
Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain.
While experimental baroreceptor stimulation is known to elicit hypoalgesia in healthy individuals, the impact of spontaneous baroreflex sensitivity (BRS) on acute pain responses is not known. We tested for associations between BRS and pain responses in healthy individuals, whether these associations are altered in chronic low back pain (CLBP), and the role of alpha-2 adrenergic (ADRA2) mechanisms in these effects. Twenty-five healthy controls and 21 CLBP subjects completed three acute pain tasks after receiving placebo or an intravenous ADRA2 antagonist (yohimbine hydrochloride, 0.4 mg/kg) across two sessions in counterbalanced order. ⋯ In contrast, CLBP subjects displayed a nonsignificant positive BRS/pain association under placebo, with yohimbine producing an inverse association similar to controls (significant for MPQ-Sensory). Results suggest presence of spontaneous BRS-related hypoalgesia in healthy individuals that is partially mediated by ADRA2 mechanisms, and that CLBP blunts BRS-related hypoalgesia. As a group, the CLBP subjects do not manifest baroreceptor-induced antinociception.