Pain
-
A workshop of the 2015 International Neuropathic Pain Congress was focused on potassium channels to propose emerging ideas on the role of these channels on pain modulation and to determine whether they can become relevant targets for designing novel analgesic compounds. Two kinds of potassium channels were particularly evoked: selected subunits of the voltage-gated potassium (Kv) and of the K2P channel families. ⋯ Throughout this review, the role of potassium channels in pain is obvious, which renders them potential targets for innovative analgesics with peripheral and/or central action depending on the channel. Clearly, some preliminary results obtained with known or novel potassium channel openers suggest that they might represent a novel class of analgesics in neuropathic pain or other pathological contexts.
-
Randomized Controlled Trial
Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury.
Chronic pain after spinal cord injury (SCI) may present as hyperalgesia, allodynia, and/or spontaneous pain and is often resistant to conventional pain medications. Identifying more effective interventions to manage SCI pain requires improved understanding of the pathophysiological mechanisms involved. Cell cycle activation (CCA) has been implicated as a key pathophysiological event following SCI. ⋯ Early administration of flavopiridol significantly shortened duration of MGS changes. Late flavopiridol intervention significantly limited hyperesthesia at 7 days after treatment, associated with reduced glial changes, but without effect on locomotion. Thus, our data suggest that cell cycle modulation may provide an effective therapeutic strategy to reduce hyperesthesia after SCI, with a prolonged therapeutic window.
-
Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. ⋯ In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.
-
Percentage of pain intensity difference (PercentPID) is a recognized way of evaluating pain relief with an 11-point numerical rating scale (NRS) but is not without flaws. A new metric, the slope of relative pain intensity difference (SlopePID), which consists in dividing PercentPID by the time between 2 pain measurements, is proposed. This study aims to validate SlopePID with 3 measures of subjective pain relief: a 5-category relief scale (not, a little, moderate, very, complete), a 2-category relief question ("I'm relieved," "I'm not relieved"), and a single-item question, "Wanting other medication to treat pain?" (Yes/No). ⋯ Considering the "very" category from the 5-category relief scale as a substantial relief, the average cutoff for substantial relief was a decrease of 64% (95% CI, 59-69) for PercentPID and of 49% per hour (95% CI, 44-54) for SlopePID. However, when a cutoff criterion of 50% was used as a measure of pain relief for an individual patient, PercentPID underestimated pain-relieved patients by 12.1% (P < 0.05) compared with the SlopePID measurement, when pain intensity at baseline was an odd number compared with an even number (32.9% vs 45.0%, respectively). SlopePID should be used instead of PercentPID as a metric to evaluate acute pain relief on a 0 to 10 NRS.
-
Pain can be modulated by contextual stimuli, such as emotions, social factors, or specific bodily perceptions. We presented painful laser stimuli together with body-related masochistic visual stimuli to persons with and without preferred masochistic sexual behavior and used neutral, positive, and negative pictures with and without painful stimuli as control. Masochists reported substantially reduced pain intensity and unpleasantness in the masochistic context compared with controls but had unaltered pain perception in the other conditions. ⋯ Masochists additionally showed negative correlations between the duration of interest in masochistic activities and activation of areas involved in motor activity and affective processing. We propose that the parietal operculum serves as an important relay station that attenuates the affective-motivational aspects of pain in masochists. This novel mechanism of pain modulation might be related to multisensory integration and has important implications for the assessment and treatment of pain.