Pain
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Conditioned pain modulation (CPM) and temporal summation of pain (TSP) are 2 experimental paradigms capturing endogenous pain modulation, which have repeatedly demonstrated clinical relevance. Conditioned pain modulation describes the inhibition of the pain response to a test stimulus (Ts) when a second noxious stimulus, the conditioning stimulus (CS), is concurrently applied. Temporal summation of pain describes the enhanced pain response to a series of stimuli compared with single stimuli. ⋯ Interestingly, this interaction was modality-dependent: TSP for heat Ts was completely abolished by CPM, whereas this was not the case for pressure Ts. Our findings suggest different forms of central sensitization induced by TSP using either heat or pressure stimuli, which differ in their susceptibility to CPM. Clinical implications and directions for future research are discussed.
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Oxytocin (OT), known for its neurohormonal effects around birth, has recently been suggested for being a critical determinant in neurodevelopmental disorders. This hypothalamic neuropeptide exerts a potent analgesic effect through an action on the nociceptive system. This endogenous control of pain has an important adaptive value but might be altered by early life stress, possibly contributing to its long-term consequences on pain responses and associated comorbidities. ⋯ The involvement of epigenetic changes in these alterations was confirmed since neonatal treatment with the histone deacetylase inhibitor SAHA, not only normalized nociceptive sensitivities but also restored OT receptor-mediated stress-induced analgesia and the endogenous antihyperalgesia in inflamed NMS rats. There is growing evidence in the literature that early life stress might impair the nociceptive system ontogeny and function. This study suggests that these alterations might be restored while stimulating OT receptor signaling or histone deacetylase inhibitors, using molecules that are currently available or part of clinical trials for other pathologies.
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Peripheral neuropathy is the major dose-limiting side effect of many currently used chemotherapies, such as vincristine (VCR). We recently demonstrated that candesartan, an angiotensin II type 1 receptor antagonist, was neuroprotective against resiniferatoxin-induced sensory neuropathy, and that this effect is mediated by stimulation of the angiotensin II type 2 receptor (AT2R). Thus, we evaluated the effect of preventive treatment with candesartan and a specific AT2R agonist, C21, on a mouse model of VCR-induced neuropathy. ⋯ Both drugs prevented VCR-induced nonpeptidergic intraepidermal nerve fiber loss. Only C21 displayed neuroprotective effects against VCR-induced loss and enlargement of myelinated nerve fibers in the sciatic nerve. Our finding that candesartan and C21 are protective against VCR-induced neuropathic pain through AT2R stimulation favors evaluation of its therapeutic potential in patients receiving chemotherapy.
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Review Meta Analysis
Catastrophizing, pain, and functional outcomes for children with chronic pain: a meta-analytic review.
Pediatric chronic pain is associated with numerous negative outcomes including increased physical disability, increased rates of depression and anxiety, and decreased quality of life (QOL). Pain catastrophizing-broadly conceptualized as including rumination, magnification, and helplessness cognitions surrounding one's pain-has been linked with poor functional outcomes in children with chronic pain. Pain catastrophizing in pediatric chronic pain is often considered a key factor on which to focus treatment efforts. ⋯ These relationships were robust, minimizing potential publication bias. None of the examined moderators were significant. The strong relationships found between catastrophizing and anxiety, depression, and QOL suggest that successfully intervening on catastrophizing could have far reaching implications in improving pain outcomes in pediatric chronic pain.
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Patellofemoral pain (PFP) is a common and recurrent knee condition in young females, characterized by pressure hyperalgesia and reduced pain inhibitory control. This study investigated antinociceptive and pronociceptive profiles in young females with long-standing (>5 years) PFP (current-PFP), those who recovered from adolescent PFP (recovered-PFP), and pain-free controls. This preregistered, assessor-blinded, cross-sectional study included 87 females younger than 25 years: 36 current-PFP, 22 recovered-PFP, and 29 pain-free controls. ⋯ Compared with controls, the recovered-PFP also had reduced pressure pain thresholds at the knee, which were higher than the current-PFP (mean difference: 110-225 kPa; P < 0.05). In conclusion, both current-PFP and recovered-PFP displayed altered pain mechanisms compared to controls with no history of knee pain, despite resolution of symptoms in the recovered-PFP group. The implications of these findings in the recurrent nature of PFP requires further studies.