Pain
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Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. However, SCS is not effective for all the patients and the mechanisms underlying the reduction in pain by SCS are not clearly understood. To elucidate the mechanisms of pain relief by SCS, we utilized the spared nerve injury model. ⋯ The effect was cumulative with a greater reversal by the fourth treatment when compared to the first treatment. Treatment with 100Hz, 250Hz or sham SCS had no significant effect on the decreased withdrawal threshold of the paw or muscle that normally occurs after nerve injury. In conclusion, SCS at 4Hz and 60Hz was more effective in reducing hyperalgesia than higher frequencies of SCS (100Hz and 250Hz); and repeated treatments result in a cumulative reduction in hyperalgesia.
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Several studies have implicated a potential role for histamine H(3) receptors in pain processing, although the data are somewhat conflicting. In the present study we investigated the effects of the novel potent and highly selective H(3) receptor antagonists GSK189254 (6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride) and GSK334429 (1-(1-methylethyl)-4-([1-[6-(trifluoromethyl)-3-pyridinyl]-4-piperidinyl]carbonyl)hexahydro-1H-1,4-diazepine) in two rat models of neuropathic pain, namely the chronic constriction injury (CCI) model and the varicella-zoster virus (VZV) model. Both GSK189254 (0.3, 3 and/or 10mg/kg p.o.) and GSK334429 (1, 3 and 10mg/kg p.o.) significantly reversed the CCI-induced decrease in paw withdrawal threshold (PWT) measured using an analgesymeter and/or von Frey hairs. ⋯ Specific binding to H(3) receptors was demonstrated with [(3)H]-GSK189254 in the dorsal horn of the human and rat spinal cord, and in human dorsal root ganglion (DRG), consistent with the potential involvement of H(3) receptors in pain processing. In conclusion, we have shown for the first time that chronic oral administration of selective H(3) antagonists is effective in reversing neuropathic hypersensitivity in disease-related models, and that specific H(3) receptor binding sites are present in the human DRG and dorsal horn of the spinal cord. These data suggest that H(3) antagonists such as GSK189254 and GSK334429 may be useful for the treatment of neuropathic pain.
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In previous studies we demonstrated that protein kinase D1 (PKD1/PKCmu) could directly phosphorylate the transient receptor potential V1 (TRPV1) at its N-terminal region and enhance the function of TRPV1 in CHO cells stably transfected with TRPV1. In the current study we assessed the involvement of PKD1 in pain modulation and explored the possible interaction between PKD1 and TRPV1 in rat inflammatory heat hypersensitivity. PKD1 was translocated to cytoplasmic membrane fraction and was trans-phosphorylated only in membrane fraction but not in cytoplasmic fraction of dorsal root ganglia (DRG) at 2 and 6h after Complete Freund's Adjuvant (CFA) treatment. ⋯ The average magnitude of the peak inward current evoked by capsaicin was greater in the DRG overexpressing PKD1 than in those expressing DN-PKD1. Furthermore, overexpressed PKD1 could up regulate, whereas PKD1 antisense could knock down TRPV1 content in DRG through posttranscriptional regulation manner. We concluded that PKD1 in DRG, through interaction with TRPV1, is involved in developing and maintaining inflammatory heat hypersensitivity.
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The purpose of this study was to verify the usefulness of an adaptation of the stress process model in organizing the psychological variables associated with the development of low-back-pain related disability. French-speaking Canadian workers on compensated sick leave (N=439) due to recent occupational low back pain (LBP) were evaluated during the sub-acute stage of LBP (between 30 and 83 days after injury). They were assessed for the following factors: life events, injury-specific cognitive appraisal, emotional distress, avoidance coping, and functional disability. ⋯ The stress model tested here reaffirms the importance of life events in the development of disability through the more established emotional distress factor. Also, cognitive appraisal appears to have an indirect effect on disability through activity avoidance and distress. This adaptation of the stress model makes it possible to integrate risk factors into a reduced set of meaningful factors and proposes a more general adaptation explanation of disability than the specific fear-avoidance model.