Clinical Pain Reduction Research Articles

Identifying oxidized lipid mediators as prognostic biomarkers of chronic posttraumatic headache.

Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of this study was to investigate whether circulating oxylipins measured in the acute setting after TBI could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days postinjury with a neurobehavioral symptom inventory (NSI) and satisfaction with life survey. Liquid chromatography-tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosahexaenoic acid (DHA), and n-6 arachidonic acid and linoleic acid. Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.

Bayesian analysis of the effect of transcranial direct current stimulation on experimental pain sensitivity in older adults with knee osteoarthritis: randomized sham-controlled pilot clinical study.

PurposePrevious studies have indicated that transcranial direct current stimulation (tDCS) with the anode over the motor cortex and the cathode over the contralateral supraorbital region is effective in reducing clinical pain in patients with chronic pain, but these studies have not focused on experimental pain sensitivity. Therefore, the aim of this study was to examine the effect of tDCS on experimental pain sensitivity in older adults with knee osteoarthritis (OA).Patients and methodsForty community-dwelling participants aged 50–70 years with knee OA pain were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 minutes (n = 20) or sham tDCS (n = 20) using a parallel group design. A multimodal quantitative sensory testing battery was completed, including heat pain, pressure pain threshold (PPT), punctate mechanical pain, and conditioned pain modulation (CPM).ResultsThe active tDCS group showed greater increases in heat pain thresholds and tolerances, PPTs, and CPM, and reductions in punctate pain. In addition, beneficial changes in experimental pain measures were associated with reductions in clinical pain. Future studies are needed to extend these findings to better understand the underlying mechanisms of tDCS as well as to optimize treatment parameters including number and duration of stimulation sessions.ConclusionOur findings demonstrate that tDCS reduces experimental pain sensitivity, and these beneficial changes in experimental pain measures were associated with reductions in clinical pain.

Point-of-Care Ultrasonography Findings and Care Use Among Patients Undergoing Ultrasound-Guided Shoulder Injections.

The aims of the study were to assess the overall reduction of pain in patients undergoing ultrasound-guided shoulder injections and to characterize the preinjection point-of-care ultrasound findings and use of clinical services postinjection including the use of magnetic resonance imaging and surgeries. Data of 172 patients who underwent ultrasound-guided subacromial subdeltoid injection or glenohumeral joint injection were reviewed for preinjection point-of-care ultrasound findings, change in pain intensity at 2 mos from baseline, and use of care at 6 mos' postinjection. Pain intensity was measured by the numeric rating scale and a dichotomous report of global impression of significant improvement in pain. Responders were defined as those with 50% or more reduction in numeric rating scale or those with global impression of 50% or more improvement. There were 141 responders among the 172 patients analyzed. Full-thickness rotator cuff tears were higher in the ultrasound-guided subacromial subdeltoid injection group when compared with the glenohumeral joint injection group (P = 0.038) and abnormal bicipital tendon findings higher in the glenohumeral joint injection group (P = 0.016). There were no significant differences in specific abnormal U findings between responders versus nonresponders. Twelve patients had a shoulder magnetic resonance imaging and four patients underwent operative interventions after the injection. Overall pain reduction after ultrasound-guided shoulder injections was favorable in the short term. There was no specific preinjection point-of-care ultrasound findings associated with clinical pain reduction after injection. Additional imaging and operative intervention after ultrasound-guided shoulder injections seemed to be relatively low.

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula.

Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development.

Vibration for Pain Reduction in a Plastic Surgery Clinic.

Patients can experience significant pain during routine procedures in the plastic surgery clinic. Methods for clinical pain reduction are often impractical, time-consuming, or ineffective. Vibration is a safe, inexpensive, and highly applicable modality for pain reduction that can be readily utilized for a wide variety of procedures. This study evaluated the use of vibration as a viable pain-reduction strategy in the clinical plastic surgery setting. Patients requiring at least 2 consecutive procedures that are considered painful were enrolled in the study. These included injections, staple removal, and suture removal. In the same patient, one half of the procedures were performed without vibration and the other half with vibration. After completing the procedures, the patients rated their pain with vibration and without vibration. The patient and the researcher also described the experience with a short questionnaire. Twenty-eight patients were enrolled in the study. Patients reported significantly less pain on the Numeric Rating Scale pain scale when vibration was used compared with the control group (p < .001). The average pain score was 3.46 without vibration and 1.93 with vibration, and vibration with injections resulted in the greatest improvement. Eighty-six percent of the patients claimed that vibration significantly reduced their pain. Vibration is an effective method of pain reduction. It significantly reduces the pain experienced by patients during minor office procedures. Given its practicality and ease of use, it is a welcome tool in the plastic surgery clinic.

Can Repeat Injection Provide Clinical Benefit in Patients with Lumbosacral Diseases When First Epidural Injection Results Only in Partial Response?

Epidural steroid injection (ESI) is known to be an effective treatment for lower back or radicular pain due to herniated intervertebral disc (HIVD) and spinal stenosis (SS). Although repeat ESI has generally been indicated to provide more pain relief in partial responders after a single ESI, there has been little evidence supporting the usefulness of repeat injections in cumulative clinical pain reduction. The purpose of this study was to determine whether repeat ESI at a prescribed interval of 2 to 3 weeks after the first injection would provide greater clinical benefit in patients with partial pain reduction than that provided by intermittent injection performed only when pain was aggravated. An Institutional Review Board (IRB)-approved retrospective chart review. Spine hospital. Two hundred and four patients who had underwent transforaminal ESI (TFESI) for treatment of lower back and radicular pain due to HIVD or SS and could be followed-up for one year were enrolled. We divided the patients into 2 groups. Group A (N = 108) comprised partial responders (NRS = 3 after first injection) who underwent repeat injection at a prescribed interval of 2 to 3 weeks after the first injection. Group B (N = 96) comprised partial responders who did not receive a repeat injection at the prescribed interval, but received repeat injections only for aggravation of pain. Various clinical data including total number of injections during one year, duration of NRS < 3 during one year (NRS < 3 duration), and time interval until aggravation of pain required additional injections after repeat injection in group A, or after first injection in group B (time to reinjection), were assessed. These data were compared between groups A and B in terms of total population, HIVD, and SS. In the whole population, the mean time to reinjection was 6.09 ± 3.02 months in group A and 3.69 ± 2.07 months in group B. The NRS < 3 duration was 9.72 ± 2.86 months and 6.2 ± 2.61 months in groups A and B, respectively. In HIVD patients, the mean time to reinjection was 5.82 ± 3.23 months in group A and 3.84 ± 2.34 months in group B, and NRS < 3 duration was 9.40 ± 3.34 months and 7.15 ± 2.40 months in groups A and B, respectively. In SS patients, the mean time to reinjection was 6.40 ± 2.85 months in group A and 3.59 ± 1.88 months in group B, and NRS < 3 duration was 9.98 ± 2.41 months and 5.52 ± 2.55 months in groups A and B, respectively. Group A had a significantly longer time to reinjection and longer NRS < 3 duration than group B in the whole population, HIVD, and SS. Retrospective design. Repeat TFESI conducted at 2- to 3-week intervals after the first injection in partial responders contributed to greater clinical benefit compared to intermittent TFESI performed only upon pain aggravation. These benefits were observed in patients with HIVD and in those with SS, irrespective of severity or location of disease.

Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients.

BackgroundFibromyalgia (FM) is a chronic, centralized pain condition characterized by alterations in the functional, chemical, and structural brain networks responsible for sensory and mood processing. Transcranial direct current stimulation (tDCS) has emerged as a potential treatment for FM. tDCS can alter functional connectivity (FC) in brain regions underneath and distant to the stimulating electrode, although the analgesic mechanisms of repetitive tDCS remain unknown. The aim of this study was to investigate how a clinically relevant schedule of tDCS sessions alters resting state FC and how these changes might relate to clinical pain.MethodsResting state functional magnetic resonance imaging data were collected from 12 patients with FM at baseline, after 5 days of sham treatment, and after 5 days of real tDCS with the anode over the left primary motor cortex (M1) and the cathode over the right supraorbital cortex. Seed to whole-brain FC analyses were performed with seed regions placed in bilateral M1, primary somatosensory cortices (S1), ventral lateral (VL) and ventral posterolateral (VPL) thalami, and periaqueductal gray (PAG).ResultsStronger baseline FC between M1–VL thalamus, S1–anterior insula, and VL thalamus–PAG predicted greater analgesia after sham and real tDCS. Sham treatment (compared with baseline) reduced FC between the VPL thalamus, S1, and the amygdala. Real tDCS (compared with sham treatment) reduced FC between the VL thalamus, medial prefrontal, and supplementary motor cortices. Interestingly, decreased FC between the VL/VPL thalamus and posterior insula, M1, and S1 correlated with reductions in clinical pain after both sham and active treatments.ConclusionsThese results suggest that while there may be a placebo response common to both sham and real tDCS, repetitive M1 tDCS causes distinct changes in FC that last beyond the stimulation period and may produce analgesia by altering thalamic connectivity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0934-0) contains supplementary material, which is available to authorized users.

Acupuncture Treatment of Chronic Low Back Pain Reverses An Abnormal Brain Default Mode Network in Correlation with Clinical Pain Relief

Acupuncture is gaining in popularity as a treatment for chronic low back pain (cLBP); however, its therapeutic mechanisms remain controversial, partly because of the absence of an objective way of measuring subjective pain. Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode network (DMN) connectivity in patients with chronic pain, and also shown that acupuncture increases DMN connectivity in pain-modulator and affective-emotional brain regions of healthy subjects. This study sought to explore how cLBP influences the DMN and whether, and how, the altered DMN connectivity is reversed after acupuncture for clinical pain. RsfMRI data from 20 patients with cLBP, before and after 4 weeks of treatment, and 10 age- and gender-matched healthy controls (without treatment) were analysed using independent components analyses to determine connectivity within the DMN, and combined with correlation analyses to compute covariance between changes in DMN connectivity and changes in clinical pain. Visual analogue scale data were assessed to rate clinical pain levels. Less connectivity within the DMN was found in patients with cLBP than in healthy controls, mainly in the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and precuneus. After acupuncture, patients' connectivities were restored almost to the levels seen in healthy controls. Furthermore, reductions in clinical pain were correlated with increases in DMN connectivity. This result suggests that modulation of the DMN by acupuncture is related to its therapeutic effects on cLBP. Imaging of the DMN provides an objective method for assessment of the effects of acupuncture-induced analgesia.

Pregabalin Rectifies Aberrant Brain Chemistry, Connectivity, and Functional Response in Chronic Pain Patients

Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

Does reducing co-contraction decrease pain in patients with knee osteoarthritis?

Does reducing co-contraction decrease pain in patients with knee osteoarthritis?

Lubiprostone does not influence visceral pain thresholds in patients with irritable bowel syndrome

In clinical trials, lubiprostone reduced the severity of abdominal pain. The primary aim was to determine whether lubiprostone raises the threshold for abdominal pain induced by intraluminal balloon distention. A secondary aim was to determine whether changes in pain sensitivity influence clinical pain independently of changes in transit time. Sixty-two patients with irritable bowel syndrome with constipation (IBS-C) participated in an 8-week cross-over study. All subjects completed a 14-day baseline ending with a barostat test of pain and urge sensory thresholds. Half, randomly selected, then received 48 μg day(-1) of lubiprostone for 14 days ending with a pain sensitivity test and a Sitzmark test of transit time. This was followed by a 14-day washout and then a crossover to 14 days of placebo with tests of pain sensitivity and transit time. The other half of the subjects received placebo before lubiprostone. All kept symptom diaries. Stools were significantly softer when taking lubiprostone compared to placebo (Bristol Stool scores 4.20 vs 3.44, P < 0.001). However, thresholds for pain (17.36 vs 17.83 mmHg, lubiprostone vs placebo) and urgency to defecate (14.14 vs 14.53 mmHg) were not affected by lubiprostone. Transit time was not significantly different between lubiprostone and placebo (51.27 vs 51.81 h), and neither pain sensitivity nor transit time was a significant predictor of clinical pain. Lubiprostone has no effect on visceral sensory thresholds. The reductions in clinical pain that occur while taking lubiprostone appear to be secondary to changes in stool consistency.

Sex differences in responses to epidural steroid injection for low back pain

Abstract Sex differences in clinical and experimental pain responses have been widely reported; however, few studies have examined sex differences in outcomes from interventional pain treatment and the predictors thereof. The aims of this study were to examine sex differences in (1) the acute pain produced by epidural steroid injections (ESIs), (2) clinical improvements in pain and pain-related psychological distress and disability after ESIs, and (3) predictors of the clinical response to ESIs. A total of 57 patients (37 menopausal women and 20 men), seen in the pain clinic of a regional medical center for ESI therapy, participated. Patients rated the painfulness of the ESI procedure itself. Also, clinical pain, depression, and disability were assessed before treatment and at 2 weeks and 2 months after the ESIs. Participants also were queried about their expectations of successful pain relief, coping strategies, and pain-related anxiety, which were examined as predictors of treatment outcome. Men reported significantly greater pain intensity and unpleasantness than women for the first injection only. All groups showed significant reductions in clinical pain, depression, and disability at 2 weeks compared to baseline, but minimal change occurred between 2 weeks and 2 months past baseline. No sex differences in the magnitude of treatment response emerged; however, specific dimensions of pain coping were associated with treatment responses in a sex-dependent manner. These findings suggest that the determinants of ESI pain and treatment outcome might differ across sex. Perspective Sex-related influences on pain responses have been widely reported, but few studies have explored sex-dependent predictors of treatment response. These findings indicate that pain coping was differentially associated with outcomes after ESI in women versus men.

Cognitive performance, mood and experimental pain before and during morphine-induced analgesia in patients with chronic non-malignant pain

This paper investigates subjective, behavioral and neurophysiological changes due to treatment with oral sustained-release morphine in six patients with severe non-malignant pain. Patients rated their mood and clinical pain on visual analog scales (VAS). Experimental pain reactions were quantified by ratings on categorial scales and evoked cerebral potentials (LEP) in response to standardized laser stimuli. A standard auditory oddball task provided reaction time (RT), errors, N1 and P2 of late auditory evoked potentials (AEP), and a P300 component. It was used to measure vigilance and cognitive performance. In parallel with clinical pain reduction, laser pain ratings and LEP amplitudes were significantly reduced. In contrast, auditory P2 and P300 amplitude were found to be even enlarged under morphine. RT and mood also failed to indicate any sedation. It is concluded that LEP indicated the analgesic morphine effects whereas late potentials and P300 from auditory stimuli reflected the perceptual-cognitive status which, instead of being deteriorated by morphine-induced sedation, improved probably due to the removal of pain as a mental stressor.

Hypnotizability and the treatment of chronic facial pain.

Abstract The Carleton University Responsiveness to Suggestion Scale (CURSS) of Spanos, Radtke, Hodgins, Bertrand 3 and Stam and Spanos, Radtke, Hodgins, Stam, and Bertrand (1983) was individually administered to a sample of 61 facial pain patients. The mean scores on the 3 CURSS suggestibility dimensions were higher than those of the college student norms. As in previous studies using the CURSS, however, objective scores were smaller when experienced involuntariness was taken into account. Observer scores of overt responses were highly related to self-scores of overt responses. The CURSS also proved a good predictor of reductions in clinical pain following a psychologically based treatment program.