Pain
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Testicular pain syndrome (TPS), defined as an intermittent or constant pain in one or both testicles for at least 3 months, resulting in significant reduction of daily activities, is common. Microsurgical denervation of the spermatic cord (MDSC) has been suggested as an effective treatment option. The study population comprised 180 TPS patients admitted to our outpatient urology clinic between 1999 and 2011. ⋯ At mean follow-up of 42.8 months, 86.2% had a ≥ 50% reduction of pain and 51.7% were completely pain free. MDSC is a valuable treatment option for TPS patients because in this study 86.2% experienced a ≥ 50% reduction of pain. To prevent superfluous diagnostics and treatment, it is mandatory to follow a systematic protocol in the treatment of TPS.
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Chronic ischemic pain in peripheral arterial disease (PAD) is a leading cause of pain in the lower extremities. A neuropathic component of chronic ischemic pain has been shown independent of coexisting diabetes. We aimed to identify a morphological correlate potentially associated with pain and sensory deficits in PAD. ⋯ Mean S100 beta levels were in the normal range but were higher in advanced disease. Patients with chronic ischemic pain had a reduced IENFD associated with impaired sensory functions. These findings support the concept of a neuropathic component in ischemic pain.
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Toll-like receptors (TLR) are known to play a role in chronic pain, from animal models and limited research in humans, but their role in interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown. Similarly, alterations of the hypothalamic-pituitary-adrenal axis have been reported in some pain conditions. Our objectives were to identify inflammatory processes that might distinguish individuals with IC/BPS from healthy controls (HC) and to examine their associations with IC/BPS symptoms. ⋯ Genitourinary pain severity (P=.008), frequency (P=.001), and pain with intercourse (P=.002) were strongly associated with TLR-4 inflammatory response. TLR-4 appears to play a central role in painful symptoms of IC/BPS patients, which may be linked to poor endogenous inflammatory control. These findings may help to identify new mechanisms in IC/BPS and lead to new therapeutic approaches.
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Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain-induced anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. ⋯ Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron-microglia interactions might be important in the pathogenesis of neuropathic pain-induced anxiety.
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Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. To better understand the physiology of human sensory neurons, we performed whole-cell patch-clamp recordings from 141 human dorsal root ganglion (hDRG) neurons from 5 young adult donors without chronic pain. Nearly all small-diameter hDRG neurons (<50 μm) displayed an inflection on the descending slope of the action potential, a defining feature of rodent nociceptive neurons. ⋯ Compared to electrically evoked action potentials, chemically induced action potentials were triggered from less depolarized thresholds and showed distinct afterhyperpolarization kinetics. These data indicate that most small/medium hDRG neurons can be classified as nociceptors, that they respond directly to compounds that produce pain and itch, and that they can be activated and sensitized by inflammatory mediators. The use of hDRG neurons as preclinical vehicles for target validation is discussed.