Opioid analgesic effects on subjective well-being in the operating theatre.

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well-being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory studies of healthy non-opioid users. This observational study determined how two commonly used opioid analgesics affected patients' subjective well-being in standard clinical practice. Day surgery patients rated how good and how anxious they felt before and after an open-label infusion of remifentanil (n = 159) or oxycodone (n = 110) in the operating theatre before general anaesthesia. One minute after drug injection, patients reported feeling intoxicated (> 6/10 points). Anxiety was reduced after opioids, but this anxiolytic effect was modest (remifentanil Cohen's d = 0.21; oxycodone d = 0.31). There was moderate to strong evidence against a concurrent improvement in well-being (Bayes factors > 6). After remifentanil, ratings of 'feeling good' were significantly reduced from pre-drug ratings (d = 0.28). After oxycodone, one in three participants felt better than pre-drug. Exploratory ordered logistic regressions revealed a link between previous opioid exposure and opioid effects on well-being, as only 14 of the 80 opioid-naïve patients reported feeling better after opioid injection. The odds of improved well-being ratings after opioids were higher in patients with previous opioid exposure and highest in patients with > 2 weeks previous opioid use (adjusted OR = 4.4). These data suggest that opioid-induced improvement of well-being is infrequent in opioid-naïve patients. We speculate that peri-operative exposure could increase risk of persistent use by rendering subsequent positive opioid effects on well-being more likely.

Slow brushing reduces heat pain in humans.

BACKGROUND: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. METHODS: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. RESULTS: Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. CONCLUSIONS: Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. SIGNIFICANCE: Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation.

A single dose of antidepressant alters eye-gaze patterns across face stimuli in healthy women.

BACKGROUND: Early neurocognitive changes in emotional processing are seen following SSRI administration, which may be involved in mechanisms of action. However, the perceptual processes underpinning these effects have not been specified. METHODS: In a double-blind, placebo-controlled eye-tracking study, we assessed the effect of single dose of citalopram (20 mg) in 25 healthy females. Face stimuli with direct and averted gaze were presented while visual scan patterns and pupil sizes were monitored. Subjective state was monitored using visual analogue scales. RESULTS: There were no significant effects of citalopram on subjective state. However, the citalopram group displayed increased saccade numbers and shorter fixation duration during face viewing compared to the placebo group. Volunteers receiving citalopram also showed reduced monitoring of the eye region irrespective of the direct or averted eye position of the stimuli. The citalopram group also showed significantly larger pupil sizes than the control group. CONCLUSIONS: These results suggest that the SSRI administration affects the perceptual processing of face stimuli. The current pattern of findings is consistent with anxiogenic-like mechanisms early on in SSRI treatment. Eye-tracking provides a novel method to characterise and detect these effects.