Human Studies

Spicy-food intake has been shown to affect various human physiological systems and diseases. This study tested the analgesia effect caused by stimulation of a spicy sensation (spicy stimulation) and explored the effect of spicy-food consumption on human basal pain sensitivity. A total of 60 healthy undergraduates were included in the primary study. Placebo and sweet stimulation were used as reference interventions. Pressure and cold-pain thresholds were measured before and after taste stimulation. The frequency of spicy-food intake was also evaluated. An additional 100 subjects were recruited to validate the results. Compared to placebo stimulation, both pressure and cold-pain thresholds increased during spicy stimulation (P<0.05). The increased thresholds remained, even when the taste stimulation residue was nearly eliminated (P<0.05). The pressure (10.0[2.1]vs.12.7[3.0]kg/cm, P<0.001) and cold-pain (4.4[1.6]vs.6.2[2.7]seconds, P=0.003) thresholds in subjects who consume spicy food ≥ 3 days/week were significantly lower than in those who consume it < 3 days/week. In the validation population, the frequency of spicy-food intake was negatively associated with subjects' pressure (β=-0.218, P=0.013) and cold-pain (β=-0.205, P=0.035) thresholds. Spicy stimulation has an analgesia effect on adults that persists even after the taste stimulation stops. Conversely, a long-term spicy diet can reduce the human basal pain threshold. TRIAL REGISTRATION: The study protocol was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Army Medical University, People's Liberation Army (identification No., 2017-023-01), and it was registered on the Chinese Clinical Trial Registry at www.chictr.org.cn (No. ChiCTR1800015053). PERSPECTIVE: This study directly examined the effects of stimulation of a spicy sensation on adult pain sensitivity and was the first to explore the relationship between long-term spicy-food intake and human pain sensitivity. The results provide evidence for future clinical pain intervention and individualized pain treatment.

To examine the distribution and patterns of opioid prescribing in the United States.

The transient receptor potential (TRP) ion channel TRPM3 functions as a noxious heat sensor and plays a key role in acute pain sensation and inflammatory hyperalgesia in rodents. Despite its potential as novel analgesic drug target, little is known about the expression, function and modulation of TRPM3 in the human somatosensory system.

Trigeminal neuralgia is defined by its clinical characteristics of paroxysmal unilateral facial pain in a well-defined territory. Distribution of the pain may be in one or several of the cutaneous and/or mucous territories of the three divisions with V2 pain being the most frequent territory followed by V3 and V1. Factors determining the distribution of pain have not yet been systematically investigated. It is now well recognized that vascular compression factor is a predominant aetiology of classical trigeminal neuralgia. In this study we aimed to find whether there is a relation between the location of the vascular compression and the peripheral distribution of the pain. Patients with classical trigeminal neuralgia in whom microvascular decompression was performed were included. Data recorded pertained to the nature of the conflict, its degree and, most importantly, location around the root: supero-median, supero-lateral or inferior. Equally, clinical data for the distribution of pain were recorded. Most of the patients 318 (89.3%) had the compression coming from above, i.e. 220 (61.7%) had compression from a supero-medial direction and 98 (27.5%) from a supero-lateral direction; inferior compression was present in 38 patients (10.7%). Distribution of the pain was significantly different according to the location of the conflict (P = 0.0005, Fisher Exact test). Odds ratios were computed for each location of compression and painful territory involved. According to the overall distribution of pain, patients with supero-medial compression had an odds ratio of 2.7 [95% confidence interval (CI) 1.66-4.41] of manifesting with V1 pain. Conversely V3 pain was less likely to occur with supero-median compression than the other types of pain (odds ratio 0.53, 95% CI 0.34-0.83). Inferior compression on the other hand was more likely to manifest with V3 pain with an odds ratio of 2.56 (95% CI 1.21-5.45). Overall V2 pain had an odds ratio close to 1 regardless of the type of compression. These findings suggest an association between the location of the neurovascular conflict with its resulting insult and the distribution of pain supporting a somatotopic view of the organization of the trigeminal root and a role of the conflict in the clinical manifestation of trigeminal neuralgia.

Prescribers are often confronted with the decision to escalate opioid doses to achieve adequate analgesia. Understanding the impact of dose escalation on pain intensity is warranted. Using a retrospective cohort study design, Veterans with chronic pain and chronic opioid therapy were identified. Opioid dose escalators (>20% increase in average morphine milligram equivalent [MME] daily dose) were compared to dose maintainers (±20% change in average MME daily dose) assessed over two consecutive 6 month windows. Pain intensity was measured by the Numeric Rating Scale (NRS). The primary analyses used linear repeated measures models among a 1:1 matched sample of escalators and maintainers matched on propensity score and within ±180 days of the index date. Sensitivity analyses were conducted using adjusted linear repeated measures models with and without incorporating stabilized inverse probability of treatment weighting (SIPTW). There were 32,420 dose maintainers and 20,767 dose escalators identified with 19,358 (93%) matched pairs. Pain scores were persistently higher among dose escalators at each 90 day time period after the index date (0-90 Days After Index Date: Dose Escalators:4.68, 95%CI: 4.64, 4.72 Dose Maintainers:4.32, 95%CI: 4.28, 4.36, p<0.0001; 91-180 Days After Index Date: Dose Escalators:4.53, 95%CI: 4.49, 4.57; Dose Maintainers:4.25, 95%CI: 4.22, 4.29, p<0.0001) but were not different in the 90 days prior to the index date (Dose Escalators:4.64, 95%CI: 4.61, 4.68; Dose Maintainers:4.59, 95%CI: 4.55, 4.63, p=0.0551). Sensitivity analyses provided similar results as the primary analyses. Opioid dose escalation among patients with chronic pain is not associated with improvements in NRS pain scores.