Pain
-
Eugenol is widely used in dentistry as a local analgesic agent, because of its ability to allay tooth pain. Interestingly, eugenol shares several pharmacological actions with local anesthetics which include inhibition of voltage-gated sodium channel (VGSC) and activation of transient receptor potential vanilloid subtype 1 (TRPV1). In the present study, we investigated the effects of eugenol on pain behaviors in orofacial area, and as an attempt to elucidate its mechanism we characterized inhibitory effects of eugenol on VGSCs in trigeminal ganglion (TG) neurons. ⋯ At cellular level, eugenol reversibly inhibited APs and VGSCs in IB(4)+/TRPV1+/Na(v)1.8+ nociceptive TG neurons (Type I-Type III) and IB(4)-/TRPV1-/Na(v)1.8- nociceptive TG neurons (Type IV). Both TTX-resistant I(Na) in Type I-Type III neurons and TTX-sensitive I(Na) in Type IV neurons were sensitive to eugenol. Taken together, these results suggest that eugenol may serve as local anesthetics for other pathological pain conditions in addition to its wide use in dental clinic.
-
Chronic pain syndromes encompass several clinical entities that frequently affect the individuals' emotional and cognitive behaviours which, in turn, can also alter pain perception. Additionally, both pain perception and motivational-affective behaviours change with increasing age. In order to evaluate the influence of age upon the interaction between chronic pain and affective/cognitive behaviours, 3-, 10- and 22-month-old rats with 1 month neuropathy (spared nerve injury, SNI model) were compared with age-matched sham-operated controls in the open field (OF; locomotor and exploratory behaviours), elevated plus-maze (EPM; anxiety-like behaviour), forced swimming (FST; depressive-like behaviour), working memory water maze (WM; spatial short-term memory), Morris water maze (MWM; spatial reference memory) and spatial reversal (behavioural flexibility) tests. ⋯ Cognitive performances in the MWM and spatial reversal tests deteriorated with age; however, the SNI lesion was only detrimental in the reversal task to mid-aged animals. Our data demonstrate that the influence of neuropathic pain on affective and cognitive behaviours is age dependent and varies with the behavioural domain that is tested. Importantly, mid-aged animals seem to be more susceptible to depression and cognitive deterioration associated to chronic pain than young and old groups.
-
Randomized Controlled Trial
Placebo analgesia induced by social observational learning.
Although it has long been known that psychosocial factors play a crucial role in placebo responses, no attempt has been made to understand if social observation shapes the placebo analgesic effect. To address this question, we compared placebo analgesia induced through social observation (Group 1) with first-hand experience via a typical conditioning procedure (Group 2) and verbal suggestion alone (Group 3). In Group 1, subjects underwent painful stimuli and placebo treatment after they had observed a demonstrator (actually a simulator) showing analgesic effect when the painful stimuli were paired to a green light. ⋯ We found that observing the beneficial effects in the demonstrator induced substantial placebo analgesic responses, which were positively correlated with empathy scores. Moreover, observational social learning produced placebo responses that were similar to those induced by directly experiencing the benefit through the conditioning procedure, whereas verbal suggestions alone produced significantly smaller effects. These findings show that placebo analgesia is finely tuned by social observation and suggest that different forms of learning take part in the placebo phenomenon.
-
Clinical Trial
Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage.
Itch evoked by cowhage or histamine is reduced or blocked by capsaicin desensitization, suggesting that pruriceptive neurons are capsaicin-sensitive. Topical capsaicin can evoke both nociceptive sensations and itch, whereas intradermal injection of capsaicin evokes only burning pain. To dissociate the pruritic and nociceptive sensory effects caused by the chemical activation of sensory neurons, chemicals were applied in a punctiform manner to the skin of the forearm using individual, heat-inactivated cowhage spicules treated with various concentrations of capsaicin (1-200 mg/ml) or histamine (0.01-100 mg/ml). ⋯ Each type of spicule also produced comparable areas of dysesthesias (enhanced mechanically evoked itch or pain) and/or skin reactions (wheal and/or flare) in surrounding skin, though inconsistently. The incidence of flare was greater in response to histamine than to capsaicin or cowhage. These results suggest the possibility that capsaicin, histamine and cowhage activate common peripheral or central neural mechanisms that mediate pruritic sensations and associated dysesthesias.