Pain
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The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. ⋯ An increase in miR-181a concomitantly resulted in significant down-regulation of GABA(Aα-1) receptor subunit gene and protein expression in adult spinal cords from rats with neonatal cystitis. Intrathecal administration of the GABA(A) receptor agonist muscimol failed to attenuate the viscero-motor response (VMR) to colon distension in rats with neonatal cystitis, whereas in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of the GABAergic system in neonatal cystitis-induced chronic pelvic pain.
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Joint pain is a common clinical problem for which both inflammatory and degenerative joint diseases are major causes. The purpose of this study was to investigate the role of CB1 and CB2 cannabinoid receptors in the behavioral, histological, and neurochemical alterations associated with joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for CB1 (CB1KO) and CB2 cannabinoid receptors (CB2KO) and transgenic mice overexpressing CB2 receptors (CB2xP). ⋯ All mouse lines developed similar histological changes after MIA intra-articular injection. Nevertheless, MIA intra-articular injection produced specific changes in the expression of cannabinoid and opioid receptor genes in lumbar spinal cord sections that were further modulated by the genetic alteration of the cannabinoid receptor system. These results revealed that CB2 receptor plays a predominant role in the control of joint pain manifestations and is involved in the adaptive changes induced in the opioid system under this pain state.
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The interaction between intensity of nociceptive stimuli and cognitive load in a concomitant task is still a challenging and complex topic. Here, we investigated the interaction between top-down factors (i.e., perceptual load), induced by a visual task, and bottom-up factors (i.e., intensity of nociceptive stimuli that implicitly modifies saliency of input). Using a new experimental paradigm, in which perceptual load is varied while laser heat stimuli of different intensities are processed; we show a significant interaction between intensity of nociceptive stimuli and perceptual load on both pain ratings and task performance. ⋯ However, under this condition, task performance was impaired, regardless of interindividual differences in motivation and pain catastrophizing. Thus, we showed that pain ratings can be reduced by increasing the load of attentional resources at the perceptual level of a non-pain-related task. Nevertheless, the disruptive effect of highly intensive nociceptive stimuli on the performance of the perceptual task was evident only under high load.
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The influence of pain descriptors and mechanical hypersensitivity on pain severity in neuropathic pain has not been well researched and is poorly understood. The aim of this study was to determine the relationship between pain severity and other factors describing chronic neuropathic pain in a large cohort of patients with self-reported neuropathic pain potentially recruited as subjects for a Phase IIa study. A questionnaire specific to the study parameters covering demographics and pain characteristics was sent to potential participants. ⋯ Having 3 or 4 pain descriptors was also strongly indicative of both moderate and severe pain. Female gender, age, and history of serious mental disorders were found to be weaker indicators of both moderate and severe pain. Given the large and varied population with many neuropathic pain diagnoses in the study, the findings are not likely to be merely chance, but are likely to reflect important relationships between pain severity and other factors in those who suffer from chronic neuropathic pain.