Pain
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Tibia fracture in rats initiates a syndrome resembling the complex regional pain syndrome type I. Accumulating evidence indicates that IL-1beta is involved in the modulation of nociceptive information and it acts as an intermediate inflammatory mediator via up-regulation of NGF. We hypothesized that IL-1beta signaling might mediate the development of the CRPS-like changes after tibial fracture, either directly or by stimulating NGF expression. ⋯ We found that: (1) IL-1ra reduced fracture-induced nociceptive sensitization, but did not decrease hindpaw edema or warmth, (2) fracture chronically up-regulated IL-1beta mRNA and protein expression in hindpaw skin keratinocytes, (3) IL-1beta intraplantar injection induced mechanical allodynia in a dose-dependent manner and stimulated keratinocyte NGF expression in the hindpaw skin, and (4) intraplantar injection of NGF-induced nociceptive sensitization. Collectively, these results indicate that cutaneous IL-1beta signaling can contribute to chronic regional nociceptive sensitization after fracture, possibly by stimulating NGF over-expression in keratinocytes. Our data also highlight the importance of the keratinocyte as the primary source of post-traumatic IL-1beta over-expression.
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In patients with phantom limb pain or complex regional pain syndrome (CRPS), sensory discrimination training increases tactile acuity, normalises cortical reorganisation and decreases pain. In healthy people, sensory cortical response, and tactile acuity, are greater if the participant looks towards the body part being stimulated. Does this effect enhance tactile training in CRPS patients? Ten patients underwent a 30-min tactile discrimination training session under four conditions (order randomised) in a 2 x 2 design: looking towards or away from the stimulated limb and seeing or not seeing skin. ⋯ Although this condition also imparted a greater reduction in resting pain at post-treatment than the other conditions, and change in pain and change in TPD over the session were strongly related (r=0.83, p<0.001), there was no residual effect on pain at 2-day follow-up. In the other conditions, tactile acuity had returned to pre-training levels at 2-day follow-up. The results should directly improve management of CRPS, and have implications for rehabilitation of other conditions associated with nervous system injury or disease, for example stroke, in which tactile recovery is a major objective of rehabilitation.
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It is widely appreciated that there is significant inter-individual variability in pain sensitivity, yet only a handful of contributing genetic variants have been identified. Computational genetic mapping and quantitative trait locus analysis suggested that variation within the gene coding for the beta3 subunit of the Na+,K+-ATPase pump (Atp1b3) contributes to inter-strain differences in the early phase formalin pain behavior. ⋯ Furthermore, in vivo siRNA knockdown of the beta3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the beta3 subunit of the Na+,K+-ATPase is a novel determinant of nociceptive sensitivity and further supports the notion that pain variability genes can have very selective effects on individual pain modalities.
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Comparative Study
Exploring relationships for visceral and somatic pain with autonomic control and personality.
The autonomic nervous system (ANS) integrates afferent and motor activity for homeostatic processes including pain. The aim of the study was to compare hitherto poorly characterised relations between brainstem autonomic control and personality in response to visceral and somatic pain. Eighteen healthy subjects (16 females, mean age 34) had recordings during rest and pain of heart rate (HR), cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), skin conductance level (SC), cardiac sympathetic index (CSI) and mean blood pressure (MBP). ⋯ Visceral pain-related parasympathetic change correlated with personality. ANS defence responses are nuanced and may relate to personality type for visceral pain. Clinical relevance of these findings warrants further exploration.
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Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. ⋯ Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb.