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Pain medications are widely prescribed to treat chronic back pain (CBP). However, the effect of using pain medications on individuals with CBP has received very little attention.
Learn More >Generalized pain hypersensitivity is frequently observed in chronic pain conditions. Currently, identification is based on expert clinical opinion, and in very few cases combined with quantitative sensory testing. The objectives of this study were to develop and evaluate a short self-report measure of generalized pain hypersensitivity: a generalized pain questionnaire (GPQ).
Learn More >Cluster headache (CH) is the most severe primary headache condition. Its pathophysiology is multifaceted and incompletely understood. This review brings together the latest neuroimaging and neuropeptide evidence on the pathophysiology of CH.
Learn More >Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluated – seven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats.
Learn More >The quality of life for millions of people worldwide is affected by chronic pain. In addition to the effect of chronic pain on well-being, chronic pain has also been associated with poor health conditions and increased mortality. Due to its multifactorial origin, the classification of pain types remains challenging. MicroRNAs (miRNA) are small molecules that regulate gene expression. They are released into the bloodstream in a stable manner under normal and pathological conditions and have been described as potential biomarkers. In the present study, we aimed to investigate whether pain may induce an aberrant, specific dysregulation of miRNA expression, depending on the origin of the pain.
Learn More >The aims of the present study were to investigate whether the association between the Central Sensitization Inventory (CSI) score, pain-related symptoms, pain-related disability, and health-related quality of life differed by disease (chronic low back pain [CLBP] vs knee osteoarthritis [KOA]), and to determine optimal cutoff scores for the CSI reflecting disease-specific characteristics. A total of 104 patients with CLBP and 50 patients with KOA were recruited. Central sensitization-related symptoms (CSI), EuroQol 5-dimension (EQ-5D), Brief Pain Inventory, widespread pain (Widespread Pain Index [WPI]), pressure pain threshold (PPT), and temporal summation (TS) were assessed and compared between the CLBP and KOA groups. Univariate correlation analysis was performed in each group. The receiver operating characteristic (ROC) curve analysis was performed to identify 1) presence/absence of central sensitization (CS), 2) presence/absence of central sensitivity syndromes (CSSs), and 3) pain intensity and pain interference in each group. The CSI and WPI scores were significantly higher in the CLBP group than in the KOA group. EQ-5D and pain interference scores significantly correlated with the CSI score in both the CLBP and KOA groups. The WPI score, PPT, and TS did not correlate with the CSI score in either the CLBP or KOA group. The suggested cutoff scores were 28 in the CLBP group and 17 in the KOA group to identify presence or absence of CSSs, and 34 in the CLBP group and 18-19 in the KOA group to identify pain severity. The impact of CS on pain could differ between CLBP and KOA and that cutoff scores differ by each parameter we attempted to identify. Therefore, we should use the appropriate cutoff scores for the purposes and consider the difference in the impact of CS on pain by the patient group.
Learn More >Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear.
Learn More >The α9 subunit of nicotinic acetylcholine receptors (nAChRs) exists mainly in heteropentameric assemblies with α10. Accumulating data indicate the presence of three different binding sites in α9α10 nAChRs: the α9(+)/α9(-), the α9(+)/α10(-), and the α10(+)/α9(-). The major role of the principal (+) side of the extracellular domain (ECD) of α9 subunit in binding of the antagonists methyllylcaconitine and α-bungarotoxin was shown previously by the crystal structures of the monomeric α9-ECD with these molecules. Here we present the 2.26-Å resolution crystal structure of α9-ECD in complex with α-conotoxin (α-Ctx) RgIA, a potential drug for chronic pain, the first structure reported for a complex between an nAChR domain and an α-Ctx. Superposition of this structure with those of other α-Ctxs bound to the homologous pentameric acetylcholine binding proteins revealed significant similarities in the orientation of bound conotoxins, despite the monomeric state of the α9-ECD. In addition, ligand-binding studies calculated a binding affinity of RgIA to the α9-ECD at the low micromolar range. Given the high identity between α9 and α10 ECDs, particularly at their (+) sides, the presented structure was used as template for molecular dynamics simulations of the ECDs of the human α9α10 nAChR in pentameric assemblies. Our results support a favorable binding of RgIA at α9(+)/α9(-) or α10(+)/α9(-) rather than the α9(+)/α10(-) interface, in accordance with previous mutational and functional data.
Learn More >Metacognitions, which are beliefs about our own thinking processes, can modulate worry and rumination and thereby influence emotional distress. This study aimed to develop a self-report measure of unhelpful pain-related metacognitions which might serve as a clinical and research tool to better understand pain catastrophizing, a significant risk factor for adverse pain outcomes. Two phases of validation are presented. Phase 1 reports on how the Pain Metacognitions Questionnaire (PMQ) was empirically developed through a qualitative study of 20 people with chronic back ( = 15) or knee ( = 5) pain in secondary or tertiary care and then validated in a large internet sample of people experiencing pain ( = 864). Rasch analysis yielded a 21-item scale with two dimensions (positive and negative metacognition) assessing how useful and problematic people believe rumination about pain to be, respectively. In Phase 2, further validation using a new sample ( = 510) replicated initial findings. Both PMQ subscales have good retest reliability ( = 0.76, = 0.72) and internal consistency (0.86, 0.87). They correlate negatively with mindfulness and positively with pain intensity, disability, anxiety, depression, catastrophizing, rumination, and metacognition. The PMQ also predicts unique variance in catastrophizing when other variables are controlled and predicts 'patient' status for pain catastrophizing. Sensitivity analysis yielded preliminary suggestions for clinically meaningful cut-offs. Unhelpful pain metacognitions can be validly and reliably measured using a self-report instrument. Future studies using the PMQ might shed new light on pain-related thinking processes to develop better interventions for people prone to worry and rumination about their pain.
Learn More >Glycine receptors (GlyRs) are chloride-permeable pentameric ligand-gated ion channels. The inhibitory activity of GlyRs is essential for many physiological processes, such as motor control and respiration. In addition, several pathological states, such as hyperekplexia, epilepsy, and chronic pain, are associated with abnormal glycinergic inhibition. Recent studies have pointed out that positive allosteric modulators targeting the GlyR α3 subunit (α3GlyR) displayed beneficial effects in chronic pain models. Interestingly, previous electrophysiological studies have shown that tropeines, which are a family of synthetic antagonists of the serotonin type 3 receptors (5-HTRs), potentiate the activity of GlyRs conformed by α1 subunits. However, despite its importance as a pharmacological target in chronic pain, it is currently unknown whether the α3GlyR function is modulated by tropeines. Using electrophysiological techniques and molecular docking simulations, here we show that tropeines are inhibitors of the α3GlyR function. Tropisetron, a prototypical tropeine, exerted concentration-dependent inhibitory effects on α3GlyRs at the low micromolar range. In addition, three other tropeines showed similar effects. Single-channel recordings show that tropisetron inhibition is associated with a decrease in the open probability of the ion channel. Molecular docking assays suggest that tropeines preferentially bind to an agonist-free, closed state of the ion channel. The tropeine binding occurs in a discrete pocket around the vicinity of the orthosteric site within the extracellular domain of α3GlyR. Thus, our results describe the pharmacological modulation of tropeines on α3GlyRs. These findings may contribute to the development of GlyR-selective tropeine derivatives for basic and/or clinical applications.
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