Pain
-
Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced N-methyl-d-aspartate (NMDA) receptor-mediated currents in spinal cord lamina II neurons. At the cellular level, the effect of leptin on spinal NMDA-induced currents was mediated through the leptin receptor and the JAK2/STAT3 (but not PI3K or MAPK) pathway, as the leptin effect was abolished in leptin receptor-deficient (db/db) mice and inhibited by a JAK/STAT inhibitor. ⋯ Our data demonstrate a relationship between leptin and NMDA receptor-mediated spinal neuronal excitation and its functional role in nociceptive behavior. Since leptin contributes to nociceptive behavior induced by nerve injury, the present findings suggest an important cellular link between the leptin's spinal effect and the NMDA receptor-mediated cellular mechanism of neuropathic pain. A functional link is demonstrated between leptin, an adipocytokine, and the cellular mechanisms of neuropathic pain via enhancement of function and expression of spinal N-methyl-d-aspartate receptors.
-
The important role of operant learning in the development and maintenance of chronic pain is widely recognized. A specific type of reinforcement based on the reduction of painful stimulation when a person's perception changes in the desired direction has been termed intrinsic reinforcement of pain. In the present study, the role of intrinsic operant learning in chronic pain was tested in fibromyalgia (FM) patients with and without comorbid irritable bowel syndrome (IBS) compared with healthy persons. ⋯ Whereas healthy persons learned perceptual changes according the experimental protocol, both patient groups failed to show normal operant perceptual learning: FM patients without IBS demonstrated sensitization learning comparable to that in healthy persons, but unexpectedly these patients learned even more pronounced sensitization in the habituation learning condition, contradicting the experimental protocol; FM patients with IBS demonstrated neither learning of enhanced sensitization nor enhanced habituation; no signs of differential operant learning were observable. Thus, operant perceptual learning was impaired in FM patients; whether learning of both enhanced perceptual sensitization and habituation was impaired depended on the presence of comorbid IBS and could not be explained by other clinical characteristics of the patients such as pain threshold, duration of pain, depressive symptoms, or anxiety. While healthy participants learned sensitization and habituation according to an operant task, FM patients without IBS showed enhanced sensitization and FM with IBS no learning.
-
Randomized Controlled Trial Clinical Trial
On the importance of placebo timing in rTMS studies for pain relief.
The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex for neuropathic pain relief is founded on double-blind studies versus placebo. In these studies, however, the analgesic effect of active interventions remained modest compared with the placebo effect. This observation led us to re-evaluate the intrinsic placebo action on pain relief according to the relative timing of active and sham rTMS interventions. ⋯ The fact that placebo effects could be enhanced by a previous rTMS with an analgesic effect as low as 10% suggests that a 30% pain decrease threshold in therapeutic trials may be too severe because smaller analgesic effects may have a clinical significance too. Sham rTMS induces significant analgesia only when preceded by a successful active stimulation. Such a placebo modulation is probably related to an unconscious conditioned learning.
-
Chronic pain is a common reason for medical visits, but prevalence estimates vary between studies and have rarely included drug treatment data. This study aimed to examine characteristics of chronic pain and its relation to demographic and health factors, and factors associated with treatment of pain with opioid analgesics. A chronic pain module was added to the 2007 Kansas Behavioral Risk Factor Surveillance System (response rate = 61%). ⋯ S. A. Overall, 45.7% of people who take prescription drugs for chronic pain reported taking opioid analgesics.
-
Glycine inhibitory dysfunction provides a useful experimental model for studying the mechanism of dynamic mechanical allodynia, a widespread and intractable symptom of neuropathic pain. In this model, allodynia expression relies on N-methyl-d-aspartate receptors (NMDARs), and it has been shown that astrocytes can regulate their activation through the release of the NMDAR coagonist d-serine. Recent studies also suggest that astrocytes potentially contribute to neuropathic pain. ⋯ These results suggest the following scenario: removal of glycine inhibition makes tactile stimuli able to activate astrocytes; activated astrocytes may provide d-serine to enable NMDAR activation and thus allodynia. Such a contribution of astrocytes to pathological pain fuels the emerging concept that astrocytes are critical players in pain signaling. Glycine disinhibition makes tactile stimuli able to activate astrocytes, which may provide d-serine to enable NMDA receptor activation and thus allodynia.