Human Studies

Opioids, which carry a high risk for addiction and overdose, are commonly prescribed after corneal surgery. Data are lacking describing opioid prescribing practices and opioid needs by patients after ophthalmic surgery.

Oral sucrose is commonly used to provide analgesia to neonates during painful procedures, such as venepuncture. The additional benefits of reducing pain during venepuncture when oral sucrose is combined with nonpharmacological strategies have not been extensively studied. This randomized controlled trial compared the efficacy of oral sucrose with nonnutritive sucking vs. oral sucrose with nonnutritive sucking plus "holding-cuddling" for pain management during venepuncture in term infants from birth to 3 months of life. Seventy-eight infants were equally randomized to receive 24% oral sucrose with nonnutritive sucking (control group) or 24% oral sucrose with nonnutritive sucking plus "holding-cuddling" (being held in a secure, cuddling position; experimental group) before venepuncture. Behavioral response to pain was measured by the 0-10 ranking scale "acute pain for neonates (APN)" at 30 and 60 s after venepuncture. Within the study sample, APN scores were ≥ 2 for 32/68 (47%) infants. "Holding-cuddling" did not significantly reduce mean APN scores at 30 and 60 s, but the rate of infants experiencing a high pain score (APN ≥ 8) at 60 s after the venepuncture was significantly lower in the experimental group compared to controls [4/34 vs. 12/34 ( = 0.04)]. Venepuncture is a painful procedure in newborn and young infants. The implementation of behavioral strategies in association with oral sucrose may mitigate pain during this procedure. This trial was registered at http://clinicaltrials.gov/ (NCT number 02803723).

Although transcranial direct current stimulation (tDCS) and mirror therapy (MT) have benefits in combating chronic pain, there is still no evidence of the effects of the simultaneous application of these techniques in patients with neuropathic pain. This study aims to assess the efficacy of tDCS paired with MT in neuropathic pain after brachial plexus injury. In a sham controlled, double-blind, parallel-group design, 16 patients were randomized to receive active or sham tDCS administered during mirror therapy. Each patient received 12 treatment sessions, 30 min each, during a period of 4 weeks over M1 contralateral to the side of the injury. Outcome variables were evaluated at baseline and post-treatment using the McGill questionnaire, Brief Pain Inventory, and Medical Outcomes Study 36-Item Short-Form Health Survey. Long-term effects of treatment were evaluated at a 3-month follow-up. An improvement in pain relief and quality of life were observed in both groups ( ≤ 0.05). However, active tDCS and mirror therapy resulted in greater improvements after the endpoint ( ≤ 0.02). No statistically significant differences in the outcome measures were identified among the groups at follow-up ( ≥ 0.12). A significant relationship was found between baseline pain intensity and outcome measures ( ≤ 0.04). Moreover, the results showed that state anxiety is closely linked to post-treatment pain relief ( ≤ 0.05). Active tDCS combined with mirror therapy has a short-term effect of pain relief, however, levels of pain and anxiety at the baseline should be considered. www.ClinicalTrials.gov, identifier NCT04385030.

Spinal manipulative therapy (SMT) helps to reduce chronic low back pain (cLBP). However, the underlying mechanism of pain relief and the neurological response to SMT remains unclear. We utilized brain functional magnetic resonance imaging (fMRI) upon the application of a real-time spot pressure mechanical stimulus to assess the effects of SMT on patients with cLBP. Patients with cLBP (Group 1, = 14) and age-matched healthy controls without cLBP (Group 2, = 20) were prospectively enrolled. Brain fMRI was performed for Group 1 at three time points: before SMT (TP1), after the first SMT session (TP2), and after the sixth SMT session (TP3). The healthy controls (Group 2) did not receive SMT and underwent only one fMRI scan. During fMRI scanning, a real-time spot pressure mechanical stimulus was applied to the low back area of all participants. Participants in Group 1 completed clinical questionnaires assessing pain and quality of life using a visual analog scale (VAS) and the Chinese Short Form Oswestry Disability Index (C-SFODI), respectively. Before SMT (TP1), there were no significant differences in brain activity between Group 1 and Group 2. After the first SMT session (TP2), Group 1 showed significantly greater brain activity in the right parahippocampal gyrus, right dorsolateral prefrontal cortex, and left precuneus compared to Group 2 ( < 0.05). After the sixth SMT session (TP3), Group 1 showed significantly greater brain activity in the posterior cingulate gyrus and right inferior frontal gyrus compared to Group 2 ( < 0.05). After both the first and sixth SMT sessions (TP2 and TP3), Group 1 had significantly lower VAS pain scores and C-SFODI scores than at TP1 ( < 0.001). We observed alterations in brain activity in regions of the default mode network in patients with cLBP after SMT. These findings suggest the potential utility of the default mode network as a neuroimaging biomarker for pain management in patients with cLBP. Chinese Clinical Trial Registry, identifier ChiCTR1800015620.

Chronic pain, particularly that following nerve injury, can occur in the absence of external stimuli. Although the ongoing pain is sometimes continuous, in many individuals the intensity of their pain fluctuates. Experimental animal studies have shown that the brainstem contains circuits that modulate nociceptive information at the primary afferent synapse and these circuits are involved in maintaining ongoing continuous neuropathic pain. However, it remains unknown if these circuits are involved in regulating fluctuations of ongoing neuropathic pain in humans.

The FUTUREPAIN study develops a short general-purpose questionnaire, based on the biopsychosocial model, to predict the probability of developing or maintaining moderate-to-severe chronic pain 7-10 years into the future.

: Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. : Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. : Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. : Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.