Pain
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Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). ⋯ Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.
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Randomized Controlled Trial
Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism.
Clinical data have accumulated showing that relative hypocortisolism, which may be regarded as a neuroendocrinological correlate of chronic stress, may be a characteristic of some functional pain syndromes. However, it has not been clarified yet whether deregulations of the hypothalamus-pituitary-adrenal (HPA) axis may directly alter pain perception and thus be causally involved in the pathophysiology of these disorders. To test this hypothesis, we performed a randomized placebo-controlled crossover trial in N=20 healthy drug-free volunteers (median age 24yrs) and analyzed the effects of metyrapone-induced hypocortisolism on quantitatively assessed basal mechanical pain sensitivity (1.5-13m/s impact stimuli), perceptual wind-up (9m/s impact stimuli at 1Hz) and temporal summation of pain elicited by inter-digital web pinching (IWP; 10N pressure stimuli for 2min). ⋯ Perceptual wind-up by contrast was reduced when cortisol synthesis was blocked (p<.05). This result is reminiscent of findings from animal studies showing a reversal of NMDA receptor activation by glucocorticoid receptor antagonists in neuropathic pain models. Our results speak in favor of a potential causal role of HPA axis alterations in pain chronicity.
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Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. ⋯ No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.
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Mental defeat is a psychological construct that has recently been applied to characterize the experience of chronic pain. Elevated levels of mental defeat have been identified in patients with chronic pain, and while its presence distinguishes treatment seeking from non-treatment seeking individuals, the link between mental defeat and disability in chronic pain is yet to be established. The current study investigated the extent to which mental defeat is associated with pain-related interference, distress and disability. ⋯ In a series of regression analyses, mental defeat emerged as the strongest predictor of pain interference, depression and psychosocial disability, whereas catastrophizing was the best predictor of sleep interference, anxiety and functional disability. These findings suggest that mental defeat may be an important mediator of distress and disability in chronic pain. Theoretical and clinical implications are discussed.