Efficacy of topical cannabinoids in the management of pain: a systematic review and meta-analysis of animal studies

Background/importanceCannabinoids are emerging as an alternative pain management option, preliminarily supported by preclinical and clinical studies. Unwanted side effects from oral or inhaled cannabinoids remain, however, a major barrier to widespread use. Peripherally acting cannabinoids (eg, topically applied) may circumvent these side effects while providing localized pain management.ObjectiveOur purpose was to systematically review the literature on the effectiveness of peripherally acting cannabinoids for pain management.Evidence reviewWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PubMed databases. Included studies examined the effect of topical/peripherally administered cannabinoids on pain ratings in humans, as well as pain-related outcomes in animals (eg, paw withdrawal). Due to a lack of trials, human studies were summarized in a narrative synthesis. Separate meta-analyses were performed for animal studies using radiant tail flick or paw withdrawal outcomes.FindingsOur search yielded 1182 studies following removal of duplicates, with 46 studies (6 human, 40 animal) included. Human studies (one randomized controlled trial and five case studies/series) reported no adverse events to topical cannabinoids and preliminary evidence of decreased pain ratings. Animal studies reporting tail flick (5) (2.81, 95% CI 1.93 to 3.69, p<0.001) and mechanical withdrawal (11) (2.74, 95% CI 1.82 to 3.67, p<0.001) reported prolonged responses (analgesia) in peripheral cannabinoid groups compared with controls.ConclusionsPreclinical animal studies provided low-quality evidence for peripherally administered cannabinoids to provide regional, antinociceptive effects. The scarcity of high-quality human studies underscores the need to translate preclinical evidence into well-controlled human trials.

Temporal–spectral signaling of sensory information and expectations in the cerebral processing of pain

The perception of pain is shaped by somatosensory information about threat. However, pain is also influenced by an individual’s expectations. Such expectations can result in clinically relevant modulations and abnormalities of pain. In the brain, sensory information, expectations (predictions), and discrepancies thereof (prediction errors) are signaled by an extended network of brain areas which generate evoked potentials and oscillatory responses at different latencies and frequencies. However, a comprehensive picture of how evoked and oscillatory brain responses signal sensory information, predictions, and prediction errors in the processing of pain is lacking so far. Here, we therefore applied brief painful stimuli to 48 healthy human participants and independently modulated sensory information (stimulus intensity) and expectations of pain intensity while measuring brain activity using electroencephalography (EEG). Pain ratings confirmed that pain intensity was shaped by both sensory information and expectations. In contrast, Bayesian analyses revealed that stimulus-induced EEG responses at different latencies (the N1, N2, and P2 components) and frequencies (alpha, beta, and gamma oscillations) were shaped by sensory information but not by expectations. Expectations, however, shaped alpha and beta oscillations before the painful stimuli. These findings indicate that commonly analyzed EEG responses to painful stimuli are more involved in signaling sensory information than in signaling expectations or mismatches of sensory information and expectations. Moreover, they indicate that the effects of expectations on pain are served by brain mechanisms which differ from those conveying effects of sensory information on pain.

The Influence of Examiner Gender on Responses to Tonic Heat Pain Assessments: A Preliminary Investigation

Background: The influence of examiner gender on pain reporting has been previously explored in both research and clinical settings. However, previous investigations have been limited, with the majority of studies employing single, static assessments of pain (e.g., cold pressor test, verbal pain ratings). The impact of examiner gender on both static and dynamic heat-based pain assessments is currently unknown.Methods: Thirty eight participants (20 females aged 24.1 ± 4.44, and 18 males, aged 24.8 ± 4.54) completed two identical testing sessions, randomized to a male and female examiner in a cross-over design. Pain sensitivity was examined using heat pain thresholds, verbal pain ratings to tonic heat, computerized visual analog scale (CoVAS) rating to tonic heat, and participant-controlled temperature (PCT) heat pain assessments.Results: Female participants reported higher verbal pain to tonic heat with a female examiner compared to male participants, with similar trends for CoVAS responses to tonic heat. Conversely heat pain thresholds and PCT were not significantly influenced by experimenter gender.Conclusions: Overall, verbal ratings were the most impacted by examiner gender, with temperature-based methods such as PCT and pain thresholds showing little to no examiner gender effects. While the gender of the examiner may be an important consideration in the measurement of sex and gender differences in pain research, the choice of pain assessment method may be of similar consequence.

An Investigation into the Effects of a Curcumin Extract (Curcugen®) on Osteoarthritis Pain of the Knee: A Randomised, Double-Blind, Placebo-Controlled Study

Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen®) or placebo. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee pain ratings, Japanese Orthopaedic Association Score for Osteoarthritic Knees (JOA), PROMIS–29, and performance-based testing comprising the 40-m fast-paced walk test, 6-min walk test, timed up-and-go test, and 30-s chair stand test. Compared to the placebo, curcumin significantly reduced the KOOS knee pain score (p = 0.009) and numeric knee pain ratings (p = 0.001). Curcumin was also associated with greater improvements (p ≤ 0.05) than the placebo on the timed up-and-go test, 6-min walk test, and the JOA total score; but not the 30-s chair stand test or 40-m fast-paced walk test. Pain-relieving medication was reduced in 37% of participants on curcumin compared to 13% on placebo. The findings support the potential efficacy of curcumin for the treatment of osteoarthritis of the knee but studies of longer duration, varying treatment doses, differing curcumin extracts, and the use of other objective outcome measures will be helpful to expand on these findings.

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls—A Mixed-Methods Study

Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls.Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software.Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they “no longer felt like themselves.” Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p &lt; 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p &lt; 0.001; Short-Form Health Survey-12), stress ratings (p &lt; 0.001; Patient Health Questionnaire-15) and functional well-being (p &lt; 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p &lt; 0.01).Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.

Effect of different Kinesio tape tensions on experimentally-induced thermal and muscle pain in healthy adults

Athletes and rehabilitation specialists have used Kinesio tape (KT) to help alleviate pain symptoms. Currently, no clear mechanism exists as to why pain is relieved with the use of KT and whether the pain relieving effect is simply a placebo effect. Additionally, the most effective taping parameters (tension of tape) for pain reduction remain unknown. We used quantitative sensory testing to address these key gaps in the KT and pain literature. Using a repeated-measures laboratory design, we examined whether KT applied at different tensions reduces experimentally-induced pain compared to a no tape condition and KT with minimal tension. Heat pain thresholds (HPT’s), pressure pain thresholds (PPT’s), and pressure pain suprathreshold (PPS: 125% of PPT) tests were administered to the forearm prior to and during KT and no tape conditions. Tape was applied to the ventral forearm at 25% of max tension, 75% of max tension, and no tension (placebo). Repeated measures ANOVA’s evaluated the pain outcomes between conditions and across time. KT had no significant effect on PPT’s and HPT’s (p’s >0.05). The ANOVA on PPS revealed that KT applied at 25% of tension significantly reduced pain ratings from the pretest (M = 34.4, SE = 5.5) to post-test 1 (M = 30.3, SE = 4.7) and post-test 2 (M = 30.4, SE = 4.7). No other conditions significantly reduced suprathreshold pressure pain. However, pain ratings at posttest-1 during the no-tape condition (M = 36.4, SE = 5.3) were significantly greater than pain ratings during post-test 1 and post-test 2 of all three tape conditions. In conclusion, the current study revealed that KT applied at low tension is the optimal tension to reduce pressure-evoked muscle pain. Additionally, the results suggested that KT applied at low, high, or no tension may acutely prevent increased muscle sensitivity with repeated pressure stimulation.

Prevalence of Preoperative Anxiety in Preoperative Patients in Nepal Police Hospital: A Cross-sectional Descriptive Study

Introduction: The possibility of undergoing anesthesia-assisted surgery can cause a great deal of anxiety in individuals. Excessive anxiety can have a number of negative consequences, including perioperative cardiac events, greater anesthetic needs, higher postoperative pain ratings, and a longer stay in the hospital. Anxiety levels during surgery might be influenced by a variety of reasons. The objective of the study was to estimate the prevalence of anxiety in adult patients scheduled for Surgery. Methods: This is Cross-sectional Descriptive Study conducted in Nepal police hospital with calculated sample size of 92 with round figure of 100, convenient sampling technique was used. Descriptive analysis was used for Analysis. Results: Prevalence of anxiety in preoperative patient was 31%. The prevalence in male patients and female patients were 21.2% and 39.5% respectively. Conclusions: When compared to many other research, the general prevalence of anxiety at Nepal Police Hospital was lower; nevertheless, the incidence was higher among female patients.

Test-retest reliability of an adaptive thermal pain calibration procedure in healthy volunteers

Quantitative sensory testing (QST) allows researchers to evaluate associations between noxious stimuli and acute pain in clinical populations and healthy participants. Despite its widespread use, our understanding of QST’s reliability is limited, as reliability studies have used small samples and restricted time windows. We examined the reliability of pain ratings in response to noxious thermal stimulation in 171 healthy volunteers (n = 99 female, n = 72 male) who completed QST on multiple visits ranging from 1 day to 952 days between visits. On each visit, participants underwent an adaptive pain calibration in which they experienced 24 heat trials and rated pain intensity after stimulus offset on a 0-10 Visual Analog Scale. We used linear regression to determine pain threshold, pain tolerance, and the correlation between temperature and pain for each session and examined the reliability of these measures. Threshold and tolerance were moderately reliable (Intra-class correlation [ICC]=0.66 and 0.67, respectively; p&lt;.001), whereas temperature-pain correlations had low reliability (ICC=0.23). In addition, pain tolerance was significantly more reliable in female participants than male participants, and we observed similar trends for other pain sensitive measures. Our findings indicate that threshold and tolerance are largely consistent across visits, whereas sensitivity to changes in temperature vary over time and may be influenced by contextual factors.

Pain expectation and avoidance in the social context: an electrophysiological study

Contingent negative variation (CNV) is an informative electrophysiological measure of pain anticipation showing higher amplitudes when highly painful stimulation is expected while presenting lower amplitudes when low painful stimulation is expected. Two groups of participants were recruited: one group expected and received an electrical stimulation of different intensities while being alone in the room (i.e. without social context), while a second group performed the same experiment with an observer in the room (i.e. with social context). Lower pain ratings and slower reaction times were observed in the group with social context and these results were accompanied in this group by a lower amplitude in the early component of the CNV as well as a lower amplitude of the later component of the wave. These results show that CNV can be considered a precise measure of central elaboration of pain anticipation explaining both its perceptual and motor components.