Pain
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Spinal nociception can be facilitated by 5-HT2 receptors in neuropathic pain. We investigated the involvement of glutamate receptors in dorsal neuron hyperexcitation that is promoted by 5-HT2B receptor (5-HT2BR) after spinal nerve ligation (SNL) in the rat. Augmentation of C-fiber-evoked potentials by spinal superfusion with 5-HT2BR agonist BW 723C86 in nerve-ligated rats was impeded by co-administration of NMDA receptor (NMDAR) antagonist D-AP5, but not by mGluR1/5 antagonist AIDA or mGluR2/3 antagonist LY 341495. ⋯ Chronic blockade of 5-HT2BR with selective antagonist SB 204741 after SNL bilaterally decreased the following: (i) PKCγ up-regulation in synaptic fraction, (ii) phosphorylation of NMDAR subunit NR1 (serine 889) in synaptic fraction, and (iii) co-localization of both PKCγ and phosphorylated NR1 with postsynaptic marker PSD-95. Chronic delivery of SB 204741 bilaterally attenuated thermal and mechanical allodynia occurring after SNL, particularly at day 2 post injury. These findings suggest that transient activation of the PKCγ/NMDAR pathway is critically involved in 5-HT2BR-mediated facilitation in the SNL model of neuropathic pain.
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Review Meta Analysis
Relationship between quantitative sensory testing and pain or disability in people with spinal pain-A systematic review and meta-analysis.
Sensitization of the nervous system can present as pain hypersensitivity that may contribute to clinical pain. In spinal pain, however, the relationship between sensory hypersensitivity and clinical pain remains unclear. This systematic review examined the relationship between pain sensitivity measured via quantitative sensory testing (QST) and self-reported pain or pain-related disability in people with spinal pain. ⋯ Fair correlations were found for the relationship between pain intensity and thermal temporal summation (0.26, 95% CI: 0.09 to 0.42) or pain tolerance (-0.30, 95% CI: -0.45 to -0.13), but only a few studies were available. Our study indicates either that pain threshold is a poor marker of central sensitization or that sensitization does not play a major role in patients' reporting of pain and disability. Future research prospects are discussed.
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The lack of efficacy of rehabilitative approaches to the management of chronic whiplash-associated disorders (WAD) may be in part due to heterogeneity of the clinical presentation of this patient population. The aim of this study was to identify homogeneous subgroups of patients with chronic WAD on the basis of symptoms of PTSD and sensory hypersensitivity and to compare the clinical presentation of these subgroups. Successive k-means cluster analyses using 2, 3 and 4 cluster solutions were performed by using data for 331 (221 female) patients with chronic (>3 months) WAD. ⋯ The nPnH cluster was the largest cluster, comprising 43.5% of the sample. The PH cluster had significantly worse disability, pain intensity, self-reported mental health status and cervical range of motion in comparison to the nPnH and nPH clusters. These data provide further evidence of the heterogeneity of the chronic WAD population and the association of a more complex clinical presentation with higher disability and pain in this patient group.
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Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. ⋯ Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR-mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury.