The journal of pain : official journal of the American Pain Society
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The study of complex regional pain syndrome (CRPS) in humans is complicated by inhomogeneities in available study cohorts. We hoped to characterize early CRPS-like features in patients undergoing hand surgery. Forty-three patients were recruited from a hand surgery clinic that had elective surgeries followed by cast immobilization. On the day of cast removal, patients were assessed for vasomotor, sudomotor, and trophic changes, and edema and pain sensitization using quantitative sensory testing. Pain intensity was assessed at the time of cast removal and after 1 additional month, as was the nature of the pain using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Skin biopsies were harvested for the analysis of expression of inflammatory mediators. We identified vascular and trophic changes in the surgical hands of most patients. Increased sensitivity to punctate, pressure, and cold stimuli were observed commonly as well. Moreover, levels of IL-6, TNF-alpha, and the mast cell marker tryptase were elevated in the skin of hands ipsilateral to surgery. Moderate-to-severe pain persisted in the surgical hands for up to 1 month after cast removal. Exploratory analyses suggested interrelationships between the physical, quantitative sensory testing, and gene expression changes and pain-related outcomes. ⋯ This study has identified CPRS-like features in the limbs of patients undergoing surgery followed by immobilization. Further studies using this population may be useful in refining our understanding of CRPS mechanisms and treatments for this condition.
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Central sensitization (CS) is a proposed physiological phenomenon in which central nervous system neurons become hyperexcitable, resulting in hypersensitivity to both noxious and non-noxious stimuli. The term central sensitivity syndrome (CSS) describes a group of medically indistinct (or nonspecific) disorders, such as fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome, for which CS may be a common etiology. In a previous study, the Central Sensitization Inventory (CSI) was introduced as a screening instrument for clinicians to help identify patients with a CSS. It was found to have high reliability and validity (test-retest reliability = .82; Cronbach's alpha = .88). The present study investigated a cohort of 121 patients who were referred to a multidisciplinary pain center, which specializes in the assessment and treatment of complex pain and psychophysiological disorders, including CSSs. A large percentage of patients (n = 89, 74%) met clinical criteria for one or more CSSs, and CSI scores were positively correlated with the number of diagnosed CSSs. A receiver operating characteristic analysis determined that a CSI score of 40 out of 100 best distinguished between the CSS patient group and a nonpatient comparison sample (N = 129) (area under the curve = .86, sensitivity = 81%, specificity = 75%). ⋯ The CSI is a new self-report screening instrument to help identify patients with CSSs, including fibromyalgia. The present study investigated CSI scores in a heterogeneous pain population with a large percentage of CSSs, and a normative nonclinical sample to determine a clinically relevant cutoff value.
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We recently showed that during acute muscle pain, C-tactile (CT) fibers mediate allodynia in healthy human subjects. In this study, we pursued the following questions: Do CTs contribute to allodynia observed in delayed onset muscle soreness (DOMS)? Is CT-mediated allodynia reproducible in a clinical pain state? In 30 healthy subjects, DOMS was induced in anterior compartment muscles of the leg by repeated eccentric contractions. DOMS was confirmed by mapping the emergence of tender points (decreased pressure pain thresholds). Furthermore, we measured pressure pain thresholds in a clinical subject who presented with activity-triggered heel pain but no resting pain. Cutaneous vibration (sinusoidal; 200 Hz-200 μm)--an otherwise innocuous stimulus--was applied to anterolateral leg before exercise, during DOMS, and following recovery from DOMS. The peripheral origin of allodynia was determined by employing conduction blocks of unmyelinated (intradermal anesthesia) and myelinated (nerve compression) fibers. In DOMS state, there was no resting pain, but vibration reproducibly evoked pain (allodynia). The blockade of cutaneous C fibers abolished this effect, whereas it persisted during blockade of myelinated fibers. In the clinical subject, without exposure to eccentric exercise, vibration (and brushing) produced a cognate expression of CT-mediated allodynia. These observations attest to a broader role of CTs in pain processing. ⋯ This is the first study to demonstrate the contribution of CT fibers to mechanical allodynia in exercise-induced as well as pathological pain states. These findings are of clinical significance, given the crippling effect of sensory impairments on the performance of competing athletes and patients with chronic pain and neurological disorders.
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Ketogenic diets (KDs) are high-fat, low-carbohydrate formulations effective in treating medically refractory epilepsy, and recently we demonstrated lowered sensitivity to thermal pain in rats fed a KD for 3 to 4 weeks. Regarding anticonvulsant and hypoalgesic mechanisms, theories are divided as to direct effects of increased ketones and/or decreased glucose, metabolic hallmarks of these diets. To address this point, we characterized the time course of KD-induced thermal hypoalgesia, ketosis, and lowered glucose in young male rats fed ad libitum on normal chow or KDs. A strict 6.6:1 (fat:[carbohydrates + protein], by weight) KD increased blood ketones and reduced blood glucose by 2 days of feeding, but thermal hypoalgesia did not appear until 10 days. Thus, ketosis and decreased glucose are not sufficient for hypoalgesia. After feeding a 6.6:1 KD for 19 days, decreased thermal pain sensitivity and changes in blood chemistry reversed 1 day after return to normal chow. Effects were consistent between 2 different diet formulations: a more moderate and clinically relevant KD formula (3.0:1) produced hypoalgesia and similar changes in blood chemistry as the 6.6:1 diet, thus increasing translational potential. Furthermore, feeding the 3.0:1 diet throughout an extended protocol (10-11 weeks) revealed that significant hypoalgesia and increased ketones persisted whereas low glucose did not, demonstrating that KD-induced hypoalgesia does not depend on reduced glucose. In separate experiments we determined that effects on thermal pain responses were not secondary to motor or cognitive changes. Together, these findings dissociate diet-related changes in nociception from direct actions of elevated ketones or decreased glucose, and suggest mechanisms with a slower onset in this paradigm. Overall, our data indicate that metabolic approaches can relieve pain. ⋯ Chronic pain is a common and debilitating condition. We show that a KD, a high-fat, very low carbohydrate diet well known for treating epilepsy, lowers sensitivity to thermal pain in rats. This reduced pain is not temporally correlated with hallmark diet-induced changes in blood glucose and ketones.
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Chronic facial muscle pain is a common feature in both fibromyalgia (FM) and myofascial (MF) pain conditions. In this controlled study, a possible difference in the mode of deregulation of the physiological response to a stressing stimulus was explored by applying an acute mental stress to FM and MF patients and to controls. The effects of the stress test were observed on pain, sympathetic variables, and both tonic and reflex electromyographic activities of masseteric and temporal muscles. The statistical analyses were performed through a generalized linear model including mixed effects. Painful reaction to the stressor was stronger (P < .001) and longer (P = .011) in FM than in MF independently of a higher pain level at baseline. The stress-induced autonomic changes only seen in FM patients did not reach significance. The electromyographic responses to the stress test were strongest for controls and weakest for FM. The stress test had no effect on reflex activity (area under the curve [AUC]) or latency, although AUC was high in FM and latencies were low in both pain groups. It is suggested that FM is characterized by a lower ability to adapt to acute stress than MF. ⋯ This study showed that an acute psychosocial stress triggered several changes in 2 pain conditions including an increase in pain of larger amplitude in FM than in MF pain. Similar stress-induced changes should be explored as possible mechanisms for differentiation between dysfunctional pain conditions.