Pain
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Persistent pain after breast cancer surgery is a common clinical problem. Given the role of potassium channels in modulating neuronal excitability, coupled with recently published genetic associations with preoperative breast pain, we hypothesized that variations in potassium channel genes will be associated with persistent postsurgical breast pain. In this study, associations between 10 potassium channel genes and persistent breast pain were evaluated. ⋯ In addition, 3 SNPs and 1 haplotype across 4 genes (ie, KCND2, KCNJ3, KCNJ6, KCNK9) were associated with membership in the Severe Pain class. These findings suggest that variations in potassium channel genes are associated with both mild and severe persistent breast pain after breast cancer surgery. Although findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.
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Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. ⋯ Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.
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Fibromyalgia (FM) is a chronic pain condition often resulting in functional impairments. Nonrestorative sleep is a prominent symptom of FM that is related to disability, but the day-to-day mechanisms relating the prior night's sleep quality to next-day reports of disability have not been examined. This study examined the within-day relations among early-morning reports of sleep quality last night, late-morning reports of pain and positive and negative affect, and end-of-day reports of activity interference. ⋯ Of note, positive affect was a stronger mediator than pain and negative affect was not a significant mediator. In summary, the findings identify 2 parallel mechanisms, pain and positive affect, through which the prior night's sleep quality predicts disability the next day in patients with FM. Furthermore, results highlight the potential utility of boosting positive affect after a poor night's sleep as one means of preserving daily function in FM.
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Fibroblast strains were derived from 2 regions of the lower genital tract of localized provoked vulvodynia (LPV) cases and pain-free controls. Sixteen strains were derived from 4 cases and 4 controls, age and race matched, after presampling mechanical pain threshold assessments. Strains were challenged with 6 separate stimuli: live yeast species (Candida albicans, Candida glabrata, Candida tropicalis, and Saccharomyces cerevisiae), yeast extract (zymosan), or inactive vehicle. ⋯ A low fibroblast IL-6 IHC(+) count may result from most IL-6 produced by fibroblasts existing in a secreted extracellular state. Enhanced, site-specific, innate immune responsiveness to yeast pathogens by fibroblasts may be an early step in LPV pathogenesis. Fibroblast strain testing may offer an attractive and objective marker of LPV pathology in women with vulvodynia of inflammatory origin.
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Randomized Controlled Trial
Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.
Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order. ⋯ In the nonpainful leg, SCS activation failed to produce an effect on TS (24 ± 20 vs 21 ± 24 in SCS "OFF" and "ON", respectively; P = 0.277). In contrast, a significant decrease in the magnitude of TS in the affected leg was observed in response to SCS activation (from 32 ± 33 to 19 ± 24; P = 0.017). These results suggest that attenuation of TS, which likely represents suppression of hyperexcitability in spinal cord neurons, is a possible mechanism underlying SCS analgesia in patients with neuropathic pain.