Heat Pain Perception Research Articles

Heat Generation and Pain Assessment in Piezosurgery Versus Conventional Drilling for Implant Placement: A Systematic Review.

The development of new technologies in implant dentistry has led to the introduction of piezosurgery, which utilizes ultrasonic vibrations for micrometric and selective bone cutting. It is hypothesized to reduce trauma to bone tissue, thereby potentially improving the healing process compared to traditional drilling methods. This systematic review examines the differences in heat generation and pain perception between piezosurgery and conventional drilling techniques for dental implant placement. An extensive review of literature was performed using various databases, includingPubMed via MEDLINE, EBSCO, and Google Scholar. Out of an initial pool of 2,279 articles, nine studies met the predefined inclusion criteria and were included in the final analysis following title and abstract screening and subsequent full-text evaluation. The quality of the selected studies was rigorously assessed using the Risk of Bias (RoB 2.0), Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I), and Quality Assessment Tool for In Vitro Studies (QUIN) tools. Data pertaining to thermal effects and postoperative pain associated with piezosurgery relative to conventional drilling protocols were collected. The results indicated a significant reduction in postoperative pain with piezosurgery; however, the technique was associated with higher intraoperative temperatures during osteotomy. These findings provide valuable insights into the potential benefits and limitations of piezosurgery in dental implant procedures.

Data-driven dynamic profiles of tonic heat pain perception in pain-free volunteers are associated with differences in anandamide levels

Our laboratory previously developed a method for assessing experimentally induced pain perception through a 2-min constant heat pain stimulation. However, the traditional analysis relying on group means struggles to interpret the considerable inter-individual variability due to the dynamic nature of the response. Recently, trajectory analysis techniques based on extended mixed models have emerged, providing insights into distinct response profiles. Notably, these methods have never been applied to pain paradigms before. Furthermore, various socio-demographic and neurobiological factors, including endocannabinoids, may account for these inter-individual differences. This study aims to apply the novel analysis to dynamic pain responses and investigate variations in response profiles concerning socio-demographic, psychological, and blood endocannabinoid concentrations. 346 pain-free participants were enrolled in a psychophysical test involving a continuous painful heat stimulation lasting for 2 min at a moderate intensity. Pain perception was continuously recorded using a computerized visual scale. Dynamic pain response analyses were conducted using the innovative extended mixed model approach. In contrast to the traditional group-mean analysis, the extended mixed model revealed three pain response trajectories. Trajectory 1 is characterized by a delay peak pain. Trajectory 2 is equivalent to the classic approach (peak pain follow by a constant and moderate increase of pain perception). Trajectory 3 is characterized by extreme responses (steep peak pain, decrease, and increase of pain perception), Furthermore, age and blood anandamide levels exhibited significant variations among these three trajectories. Using an innovative statistical approach, we found that a large proportion of our sample had a response significantly different from the average expected response. Endocannabinoid system seems to play a role in pain response profile.

Age-associated changes in multimodal pain perception.

Pain sensitivity varies across multimodal somatosensory stimuli that can rely on different conductive fibres, which, when damaged, will lead to neuropathies. However, there is limited research examining the characteristics of perceived pain, particularly as affected by the ageing process, as induced by various somatosensory stimuli that may rely on small or large fibres. Using heat and pressure stimuli on small and large fibres separately on both younger and older adults, this study examined age-associated changes in pain perception by measuring self-reported pain sensitivity, pain threshold and pain discriminability. Heat pain threshold was significantly positively correlated with age, but not pressure pain threshold. Pain threshold increased and pain discriminability decreased in response to heat stimuli in the older participants compared with the younger ones. An age-associated decline in heat pain perception was observed, suggesting an earlier degradation of heat perception. These findings provide new insight into understanding and assessing somatosensory disorders, which can help ageing populations better maintain healthy sensory functioning.

Subcutaneous Oxytocin Injection Reduces Heat Pain: A Randomized-Controlled Trial

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local. In human studies, intravenous OT has reduced visceral pain, and subcutaneous injection of OT has reduced postsurgical pain. However, the local effects of subcutaneous OT on experimental pain have not been studied. We conducted a 2-session crossover study during which healthy adults received a subcutaneous injection of synthetic OT (4 mcg/2 mL) or saline placebo (isotonic saline 2 mL), in a randomized and double-blinded manner. Eighteen participants completed full study procedures. We hypothesized that 10 minutes after injection, OT would reduce measures of acute mechanical pain, pressure pain, and heat pain perception. Subcutaneous OT significantly reduced ratings of heat pain intensity and unpleasantness (both P < .01), but did not alter mechanical pain, pressure pain, or heat pain threshold (all P > .05). Changes in heat pain were observed only on the injected arm and not on the contralateral arm, confirming a localized mechanism. These findings confirm the ability of OT in or near the skin to modulate nociceptive processes in cutaneous tissues in human adults, opening exciting avenues for further mechanistic research as well as potential clinical applications for acute pain. PerspectiveThis randomized-controlled trial showed that a subcutaneous injection of OT could reduce perception of heat pain tested with a thermode. OT did not alter mechanical or pressure pain or thresholds for perceiving heat pain. These findings are relevant to scientists and clinicians seeking nonaddictive local drug treatments for pain.

Somatosensory dysfunction in patients with posttraumatic headache: A systematic review.

Aim of the review is to summarize the knowledge about the sensory function and pain modulatory systems in posttraumatic headache and discuss its possible role in patients with posttraumatic headache. Posttraumatic headache is the most common complication after traumatic brain injury, and significantly impacts patients' quality of life. Even though it has a high prevalence, its origin and pathophysiology are poorly understood. Thereby, the existing treatment options are insufficient. Identifying its mechanisms can be an important step forward to develop target-based personalized treatment. We searched the PubMed database for studies examining pain modulation and/or quantitative sensory testing in individuals with headache after brain injury. The studies showed heterogenous alterations in sensory profiles (especially in heat and pressure pain perception) compared to healthy controls and headache-free traumatic brain injury-patients. Furthermore, pain inhibition capacity was found to be diminished in subjects with posttraumatic headache. Due to the small number of heterogenous studies a distinct sensory pattern for patients with posttraumatic headache could not be identified. Further research is needed to clarify the underlying mechanisms and biomarkers for prediction of development and persistence of posttraumatic headache.

Local and Systemic Analgesic Effects of Nerve-Specific Acupuncture in Healthy Adults, Measured by Quantitative Sensory Testing.

This study aims to assess whether acupuncture analgesia's effects are local or systemic and whether there is a dose response for these effects. Twenty-eight healthy volunteers aged 18-45 were randomized to two doses of acupuncture using points closely associated with peripheral nerves in the legs. The lower-dose group involved acupoints overlying the deep peroneal nerve (DP), and the higher-dose involved acupoints overlying the deep peroneal and posterior tibial nerves (DPTN). Baseline and acupuncture quantitative sensory testing (QST) assessments were obtained locally in the calf and great toe and systemically in the hand. Results were analyzed using factorial repeated-measures analysis of variance for each of the QST variables-cold detection threshold (CDT), vibration detection threshold (VDT), heat pain threshold (HP0.5), and heat pain perception of 5/10 (HP5.0). Location (leg/hand) and time (baseline/acupuncture) were within-subject factors. Intervention (DP/DPTN) was a between-subject factor. CDT was increased in the calf (P < 0.001) and in the hand (P < 0.001). VDT was increased in the toe (P < 0.001) but not in the hand. HP0.5 was increased in the calf (P < 0.001) and in the hand (P < 0.001). HP5.0 was increased in the calf (P = 0.002) and in the hand (P < 0.001), with the local effect being significantly greater than the systemic (P = 0.004). In all of the above QST modalities, there was no difference between the low-dose (DP) and high-dose (DPTN) acupuncture groups. Acupuncture caused comparable local and systemic analgesic effects in cold detection and heat pain perception and only local effects in vibration perception. There was no clear acupuncture dose response to these effects.

New life for an old idea: Assessing tonic heat pain by means of participant controlled temperature

BackgroundTemporal changes of pain perception to prolonged tonic heat pain are conventionally assessed using a computerized visual analog scale. Such a rating-based approach is, however, prone to floor and ceiling effects, which limit the assessment of temporal changes in perception. Thus, alternative methods that overcome these shortcomings are warranted. New methodThe aim of this study was to assess the feasibility and reliability of a psychophysical approach, i.e., participant-controlled temperature (PCT), to evaluate ongoing human perception of tonic heat pain. Fifty participants were presented with a 45 °C stimulus on the non-dominant hand, and were instructed to maintain their initial sensation for two minutes via a feedback controller in the dominant hand. A subset of participants (n = 17) performed PCT tonic heat protocols on two different days to determine the test-retest reliability. As participants controlled temperature to maintain a stable pain perception, any adjustments made reflected shifts in their perception of heat. ResultsIn 33 (71.7%) participants, we observed an initial adaptation (participant increased temperature) followed by temporal summation of pain (participant decreased temperature). Twelve participants (26.1%) showed only adaptation and one (2.2%) only temporal summation. No sex differences were observed, nor did the initial rating of pain have an effect on PCT outcomes. Temporal summation of pain showed moderate to substantial reliability upon retest. ConclusionsPCT represents can be reliably performed using a contact heat stimulator to measure the temporal summation of pain. The standardized setup and overall good reliability of the outcome measures facilitate a sound implementation into the clinical work-up of patients with pain conditions.

Effect of catechol-O-methyltransferase (rs4680) single-nucleotide polymorphism on opioid-induced hyperalgesia in adults with chronic pain.

The catechol-O-methyltransferase Val158Met polymorphism has been associated with alterations in pain perception, but the influence of the polymorphism on pain perception in patients with chronic pain receiving daily opioid therapy has not been previously reported. The primary aim of this study was to investigate the effects of the catechol-O-methyltransferase Val158Met polymorphism on heat pain perception in a cohort of adults receiving daily opioid therapy for chronic pain. Adults with chronic pain consecutively admitted to an outpatient pain rehabilitation program who met inclusion criteria and were receiving daily opioid therapy were recruited for study participation (N = 142). Individuals were genotyped for catechol-O-methyltransferase Val158Met (rs4680), and the polymorphism was analyzed using an additive and codominant genotype models. The distribution of the Val158Met genotypes was 25% for Val/Val, 41% for Val/Met and 34% for Met/Met (Hardy–Weinberg, P > 0.05). A main effect of genotype was observed for heat pain perception (P = 0.028). Under the codominant model of allele effects, exploratory post hoc pairwise comparisons adjusted for morphine equivalent dose and pain catastrophizing demonstrated that individuals with the Val/Met genotype were hyperalgesic compared to individuals with the Val/Val (P = 0.039) and Met/Met (P = 0.023) genotypes. No significant association was observed between heat pain perception and genotype under the additive model of allele effects. Among patients with chronic pain who were receiving daily opioids, the Val/Met genotype was associated with hyperalgesia using a measure of heat pain perception that has been previously indicative of opioid-induced hyperalgesia in other heterogeneous samples of adults with chronic pain. This study contributes to the emerging understanding of how catechol-O-methyltransferase activity affects pain perception in the context of daily opioid use, and these findings may be useful in the design of future trials aimed at investigating the potential efficacy of ß-2 adrenergic receptor antagonism for opioid-induced hyperalgesia.

NEO6860, modality-selective TRPV1 antagonist: a randomized, controlled, proof-of-concept trial in patients with osteoarthritis knee pain

Introduction:NEO6860 is a TRPV1 antagonist when activated by capsaicin but not by heat or pH, developed to relieve pain without the adverse events reported with non–modality-selective TRPV1 antagonists.Objective:The primary Objective of this study was to evaluate the analgesic efficacy and safety of NEO6860 after 1 day oral dosing in patients with Kellgren-Lawrence stage I, II or III osteoarthritis of the knee.Method:This randomized, double-blinded, 3-period crossover, phase II study compared 1 day (2 doses) of NEO6860 (500 mg twice a day), placebo, and naproxen in 54 patients with osteoarthritis knee pain. Primary endpoint was reduction in pain intensity (PI) on Numerical Rating Scale after exercise, using the staircase test, 8 hours after dose.Results:Level of PI, compared with baseline, was numerically lower during NEO6860 and naproxen periods vs placebo at 3 and 24 hours, but not at 8 hours after first dose. A statistically significant effect for naproxen and a trend for NEO6860 were observed at 3 and 24 hours. Least square means' (95% confidence interval) change in PI at 24 hours was −0.67 (−1.09 to −0.26), −0.97 (−1.39 to −0.55), −0.29 (−0.71 to 0.13) for NEO6860, naproxen, and placebo, respectively. NEO6860 exposure was ∼1.6 times higher compared with previous phase I. In this study, NEO6860 safety profile was less favorable than naproxen or placebo. Possibly NEO6860-related adverse events included: feel hot, headache, nausea, dizziness, fatigue, hypoaesthesia, and increased blood pressure.Conclusion:In this exploratory study, NEO6860 did not statistically significantly outperform placebo but showed an analgesic trend, without impacting body temperature and heat pain perception. Further studies are warranted to explore the potential of NEO6860 in other pain indications. We intent to optimize the dose and evaluate analgesic synergism with other mechanism.

Differential Classical Conditioning of the Nocebo Effect: Increasing Heat-Pain Perception without Verbal Suggestions.

Background: Nocebo effects, including nocebo hyperalgesia, are a common phenomenon in clinical routine with manifold negative consequences. Both explicit expectations and learning by conditioning are known to induce nocebo effects, but the specific role of conditioning remains unclear, because conditioning is rarely implemented independent of verbal suggestions. Further, although pain is a multidimensional phenomenon, nocebo effects are usually assessed in subjective ratings only, neglecting, e.g., behavioral aspects. The aim of this study was to test whether nocebo hyperalgesia can be learned by conditioning without explicit expectations, to assess nocebo effects in different response channels, and to exploratively assess, whether contingency awareness is a necessary condition for conditioned nocebo hyperalgesia.Methods: Twenty-one healthy volunteers were classically conditioned using painful and non-painful heat stimuli that followed two different cues. The conditioned nocebo effect was assessed by subjective ratings of perceived stimulation intensity on a visual analog scale and a behavioral discrimination task, assessing sensitization and habituation in response to the same stimulation following the two cues.Results: Results show a conditioned nocebo effect indicated by the subjective intensity ratings. Conditioned effects were also seen in the behavioral responses, but paradoxically, behavioral responses indicated decreased perception after conditioning, but only for subjects successfully conditioned as indicated by the subjective ratings. Explorative analyses suggested that awareness of the contingencies and the different cues was not necessary for successful conditioning.Conclusion: Nocebo effects can be learned without inducing additional explicit expectations. The dissociation between the two response channels, possibly representing the conditioned and a compensatory response, highlights the importance of considering different outcomes in nocebo responses to fully understand underlying mechanisms. The present results challenge the role of explicit expectations in conditioned nocebo effects and are relevant with implications in clinical contexts, e.g., when transient adverse effects become conditioned.

Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation

Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation.

Pain perception in healthy volunteers: effect of repeated exposure to experimental systemic inflammation.

We aimed to study the relationship between pain perception and cytokine release during systemic inflammation. We present a randomized crossover trial in healthy volunteers (n = 17) in 37 individual trials. Systemic inflammation was induced by an i.v. bolus of Escherichia coli LPS (2 ng/kg) on two separate trial days, with or without a nicotine patch applied 10 h previously. Pain perception at baseline, and 2 and 6 h after LPS was assessed by pressure algometry and tonic heat stimulation at an increasing temperature (45-48℃) during both trials. Compared with baseline, pain pressure threshold was reduced 2 and 6 h after LPS, while heat pain perception was accentuated at all testing temperatures after 2 but not 6 h. The magnitude of changes in pain perception did not correlate to cytokine release. No effect of transdermal nicotine or training status was observed. In conclusion, LPS administration in healthy human volunteers leads to reduction in pain pressure threshold and an increase in pain perception to heat stimuli, supporting a relationship between acute systemic inflammation and pain perception.

Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study.

The hormone oxytocin has been hypothesized to influence the emotional dimension of pain. This randomized, placebo-controlled, double-blind, crossover study explored whether intranasal oxytocin and emotional context can affect heat pain perception in 30 healthy male volunteers. After receiving 36 IU oxytocin or placebo, participants underwent functional Magnetic Resonance Imaging (fMRI) during which noxious and non-noxious thermode heat stimuli were applied. Simultaneously, scenes from the International Affective Pictures System (IAPS) with positive, neutral, and negative emotional valence were shown. Heat intensity and unpleasantness ratings were obtained. The activity of whole-brain correlates of heat processing was quantified via multi-voxel pattern analysis. We observed no appreciable main effects of oxytocin on ratings or neural pain correlates. Effects of emotional picture valence on ratings were smaller than reported in previous studies. Nevertheless, oxytocin was found to significantly enhance the influence of picture valence on unpleasantness ratings at noxious heat levels. No corresponding changes in whole-brain correlates of heat intensity processing were found. Our study provides evidence that intranasal oxytocin increases the effects of emotional context on the subjective unpleasantness of experimental heat pain. Future studies are needed to determine whether this effect can be utilized in clinical settings.

The role of peripheral afferents in persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial of ultrasound-guided tender point blockade

BackgroundSevere, persistent inguinal postherniorrhaphy pain (PIPP) is a debilitating condition that develops in 2–5% of patients. PIPP may be neuropathic in nature, yet the lesion in the peripheral nervous system has not been located. Most PIPP-patients demonstrate a tender point (TP) in the medial aspect of the inguinal region that triggers pain upon minimal pressure. As TPs may play a role in the pathophysiology of PIPP, the aim of this trial was to investigate the analgesic effects of local anaesthetic TP-blockade. MethodsA randomized, double-blind, placebo-controlled, crossover trial was performed in 14 PIPP-patients and six healthy volunteers. All participated in two sessions, seven days apart, receiving 10 ml of 0.25% bupivacaine or normal saline via an ultrasound-guided fascial plane block at the TP. The TP-area was used for pain assessments (at rest, on movement, with 100 kPa pressure-algometry) and quantitative sensory testing (pressure pain thresholds, thermal detection/pain thresholds, supra-threshold heat perception), before and after the TP-blockade. ResultsThe median (95% CI) reduction in pain was 63% (44.1 to 73.6%) after bupivacaine compared with 36% (11.6 to 49.7%; P+0.003) after placebo. Significant increases in cool detection (P+0.01) and pressure pain thresholds (P+0.009) with decreases in supra-threshold heat pain perception (P+0.003) were seen after bupivacaine only. In four out of six volunteers, increased thermal and evoked-pain thresholds after bupivacaine compared with placebo, was demonstrated. ConclusionsThis trial demonstrates that peripheral afferent input from the TP-area is important for maintenance of spontaneous and evoked pain in PIPP. Clinical trial registrationNCT02065219.

Pain Catastrophizing and Anxiety are Associated With Heat Pain Perception in a Community Sample of Adults With Chronic Pain.

The principle aim of this study was to investigate the associations between heat pain (HP) perception, pain catastrophizing, and pain-related anxiety in a heterogenous cohort of community-dwelling adults with chronic pain admitted to a 3-week outpatient pain rehabilitation program. All adults consecutively admitted to an outpatient pain rehabilitation program from July 2009 through January 2011 were eligible for study recruitment (n=574). Upon admission, patients completed the Pain Catastrophizing Scale (PCS), the short version of the Pain Anxiety Symptoms Scale (PASS-20), and HP perception was assessed using a standardized quantitative sensory testing (QST) method of levels. Greater PCS scores were significantly correlated with lower standardized values of HP threshold (HP 0.5) (P=0.006) and tolerance (HP 5) (P=0.003). In a multiple variable model adjusted for demographic and clinical factors known to influence HP perception, every 10-point increase in the PCS was associated with a -0.124 point change in HP 0.5 (P=0.014) and a -0.142 change in HP 5 (P=0.014) indicating that participants with higher PCS scores had lower HP thresholds and tolerances, respectively. Similarly, greater PASS-20 scores significantly correlated with lower standardized values of HP 0.5 and HP 5. In a multiple variable model, every 10-point increase in the PASS-20 was associated with a -0.084 point change in HP 0.5 (P=0.005) and a -0.116 point change in HP 5 (P=0.001) indicating that participants with higher PASS-20 scores had lower HP thresholds and tolerances, respectively. The findings of this study extend the use of a standardized method for assessing HP in a heterogenous sample of adults with chronic pain. Although pain catastrophizing shares significant variance with pain-related anxiety, our findings suggest that either measure would be appropriate for use in future studies that incorporate the QST method of levels.

Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults

ABSTRACTPrevious studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm2 Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0–100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage.

Chronic spontaneous pain is a clinically relevant non-motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5years). Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. 'Off-drug' MSA (n=11) and PD (n=14) patients selected at an early stage of the disease were compared to healthy controls (HC, n=27). MSA patients had either parkinsonian (MSA-P, n=5) or cerebellar (MSA-C, n=6) subtypes. Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA-P and MSA-C patients did not differ, either. Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information. WHAT DOES THIS STUDY ADD?: This study investigated experimental pain sensitivity at an early stage in MSA and PD.

Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study

Background: Persistent pain after breast cancer surgery (PPBCS) affects 25 – 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. Objectives: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. Study Design: This prospective pilot study was performed in 2 parts: Part 1 determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. Setting: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. Methods: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic ultrasonography to establish the sonoanatomy of the ICBN. Part 2: Six patients with PPBCS who had pain in the axilla and upper arm were recruited for the study. Summed pain intensity (SPI) scores and sensory function were measured before and 30 minutes after the block was administered. SPI is a combined pain score of numerical rating scale (NRS) at rest, movement, and 100kPa pressure applied to the maximum point of pain using pressure algometry (max = 30). Sensory function was measured using quantitative sensory testing, which consisted of sensory mapping, thermal thresholds, suprathreshold heat pain perception as well as heat and pressure pain thresholds. The ICBN block was performed under ultrasound guidance and 10 mL 0.5% bupivacaine was injected. Outcome Assessment: The ability to perform the ICBN block and its analgesic and sensory effects. Results: Only the second intercostal space could be seen on ultrasound which was adequate to perform the ICBN block. The mean difference in SPI was -9 NRS points (95%CI: -14.1 to -3.9), P = 0.006. All patients had pre-existing areas of hypoesthesia which decreased in size in 4/6 patients after the block. Limitations: The main limitation of this pilot study is its small sample size, but despite this, a statistically significant effect was observed. Conclusion: We have successfully managed to block the ICBN using ultrasound guidance and demonstrated an analgesic effect in patients in PPBCS calling for placebo-controlled studies. Key words: Anesthesia, local; intercostobrachial nerve; mastectomy; nerve block; neuralgia

A Brief Mindfulness Meditation Training Increases Pain Threshold and Accelerates Modulation of Response to Tonic Pain in an Experimental Study.

Research shows that mindfulness meditation (MM) affects pain perception; however, studies have yet to measure patterns of change over time. We examined effects of MM on perception of experimental heat pain using multiple psychophysical indices, including pattern of change in response to tonic painful stimuli. We also tested the potential moderating role of baseline mindfulness. Forty participants were randomly assigned to a brief MM training or control group. We assessed: a) heat pain threshold (HPT), b) temperature which induces pain at a fixed, target intensity level, and c) response pattern over time to tonic heat pain. Compared to control group, the MM group showed increased HPT and more rapid attenuation of pain intensity for tonic pain stimuli. Moderation analyses indicated that baseline mindfulness moderated effects of MM on HPT. A brief MM intervention appears to affect perception of experimental pain both by increasing pain threshold and accelerating modulation of response. Findings may help elucidate mechanisms of MM for chronic pain.

Salivary Alpha-Amylase Correlates with Subjective Heat Pain Perception.

Self-reports of pain are important for an adequate therapy. This is a problem with patients and infants who are restricted in providing an accurate verbal estimation of their pain. Reliable, real-time, economical, and non-invasive physiological correlates might contribute to a more comprehensive description of pain. Salivary alpha-amylase constitutes one candidate biomarker, which reflects predominantly sympathetic nervous system alterations under stressful conditions and can be measured non-invasively. The current study investigated the effects of acute heat pain on salivary alpha-amylase activity. Heat pain tolerance was measured on the non-dominant forearm. Participants completed visual analog scales on pain intensity and unpleasantness. Saliva samples were collected directly after pain induction. Twenty-seven healthy volunteers were recruited for this study. While salivary alpha-amylase levels correlated positively with intensity and unpleasantness ratings in response to acute heat pain stimuli, there was no corresponding association with pain tolerance. Salivary alpha-amylase is suggested to be an indirect physiologic correlate of subjective heat pain perception. Future studies should address the role of salivary alpha-amylase depending on the origin of pain, the concerned tissue, and other pain assessment methods.