Effects of Electroacupuncture on Opioid Consumption in Patients with Chronic Musculoskeletal Pain: A Multicenter Randomized Controlled Trial.

OBJECTIVES: To evaluate the efficacy and safety of electroacupuncture in reducing opioid consumption in patients with chronic musculoskeletal pain. DESIGN: A randomized, participant-assessor-blinded, three-arm trial. SETTING: Participants from three pain clinics and from the public. SUBJECTS: One hundred and eight adults with chronic pain who were taking opioids. METHODS: All participants received pain and medication management education. Participants were randomly allocated to electroacupuncture (N = 48), sham electroacupuncture (N = 29), or education alone (N = 31) to receive relevant treatment for 12 weeks. The last group received electroacupuncture during the three-month follow-up. Analysis of covariance and paired t tested were used. RESULTS: Opioid dosage, that is, the primary outcome measure, was reduced by 20.5% (P < 0.05) and 13.7% (P < 0.01) in the two acupuncture groups and by 4.5% in the education group at the end of the treatment phase, but without any group difference. Intensity of pain of all three groups did not change over time. No group differences were found in dosage of nonopioid analgesics, pain intensity, function, and opioid-related adverse events. During follow-up, the education group had a 47% reduction of opioids after a course of electroacupuncture. Adverse events to electroacupuncture were minor. CONCLUSION: It is safe to reduce opioid medication use in patients with chronic pain. Due to the small sample size, we could not confirm if electroacupuncture offers extra benefit in addition to education. This nondrug therapy could be a promising adjunct to facilitate opioid tapering in patients who are willing to reduce opioids.

Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson's disease?

Plastic changes within the striatum resulting from pulsatile dopaminergic stimulation are thought to lead to dyskinesia in patients with Parkinson's disease (PD). The basal ganglia play a role in processing pain. We hypothesized that the plastic changes that lead to dyskinesia may also mediate pain responses. Our objective was to compare the change in pain sensitivity after levodopa administration between stable responders, fluctuators without dyskinesia, and dyskinetic patients, and to compare pain sensitivity between PD and healthy subjects. Fifty patients with PD were assessed with cold water immersion after overnight withdrawal of dopaminergic medications and again after a standard levodopa challenge, and carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. Twenty age-matched controls were also tested. PD patients "off"-medication had a lower threshold (P = 0.016) and tolerance (P < 0.0001) to cold pain compared to controls. After levodopa administration, dyskinetic patients experienced a large increase in cold pain threshold (48%) and tolerance (66%) that was absent in stable responders (P = 0.038 and P = 0.015); there was no significant difference in pain sensitivity change scores between the fluctuator and either the stable responder or dyskinetic groups. Our results suggest that dyskinesia and pain may share common pathophysiological mechanisms in PD.

The relationship between medical comorbidity and self-rated pain, mood disturbance, and function in older people with chronic pain.

BACKGROUND: Aging is associated with greater risk for many illnesses and the prospect of multiple, concurrent disease states. Chronic pain is also very common in advanced age, and there is likely to be a relationship with comorbid burden, but few studies have examined this issue. This study tests the hypothesis that comorbid burden is associated with greater levels of self-reported pain and associated disturbance in mood and function. METHODS: Psychometric and medical data were collected from 562 patients (mean age = 76.3 years) attending a geriatric pain clinic. The number of categories endorsed on the Cumulative Illness Rating Scale (CIRS) score was used to measure accumulated comorbid burden. These groups were tested for differences in the severity of self-reported pain. The predictive capacity of comorbid burden for explaining variance in mood disturbance and functional disability was assessed after controlling for any differences in age and severity of pain. RESULTS: Over 50% of the sample had three or more comorbid problems. Groups with greater levels of comorbidity scored higher on the Present Pain Intensity Index, the sensory and affective subscales of the McGill Pain Questionnaire. Multiple regression analysis showed that the CIRS score explained a significant proportion of the variance in scores on the Geriatric Depression Scale (4.1%), Human Activities Profile (4.8%), and the physical domain of the Sickness Impact Profile (5.9%). CONCLUSION: Greater levels of comorbidity are associated with reports of more severe pain, more depressive symptoms, reduced activity levels, and higher physical impact from pain.

An interdisciplinary expert consensus statement on assessment of pain in older persons.

This paper represents an expert-based consensus statement on pain assessment among older adults. It is intended to provide recommendations that will be useful for both researchers and clinicians. Contributors were identified based on literature prominence and with the aim of achieving a broad representation of disciplines. Recommendations are provided regarding the physical examination and the assessment of pain using self-report and observational methods (suitable for seniors with dementia). In addition, recommendations are provided regarding the assessment of the physical and emotional functioning of older adults experiencing pain. The literature underlying the consensus recommendations is reviewed. Multiple revisions led to final reviews of 2 complete drafts before consensus was reached.

Acupuncture for Frequent Migraine: A Randomized, Patient/Assessor Blinded, Controlled Trial with One-Year Follow-Up.

Objectives. This study aimed to evaluate the efficacy and safety of manual acupuncture as a prophylaxis for frequent migraine. Methods. Fifty frequent migraineurs were randomly allocated to receive 16 sessions of either real acupuncture (RA = 26) or sham acupuncture (SA = 24) during 20 weeks. The primary outcomes were days with migraine over four weeks, duration, and intensity of migraine and the number of responders with more than 50% reduction of migraine days. The secondary outcomes were the relief medication, quality of migraine, quality of life, and pressure pain thresholds. Results. The two groups were comparable at baseline. At the end of the treatment, when compared with the SA group, the RA group reported significant less migraine days (RA: 5.2 ± 5.0; SA: 10.1 ± 7.1; P = 0.008), less severe migraine (RA: 2.18 ± 1.05; SA: 2.93 ± 0.61; P = 0.004), more responders (RA: 19 versus SA: 7), and increased pressure pain thresholds. No other group difference was found. Group differences were maintained at the end of the three-month follow-up, but not at the one-year follow-up. No severe adverse event was reported. Blinding was successful. Discussion. Manual acupuncture was an effective and safe treatment for short-term relief of frequent migraine in adults. Larger trials are warranted.

Cognitive factors and the experience of pain and suffering in older persons.

Cognitive factors are thought to play an important mediational role between pain and consequent levels of suffering, yet there has been little investigation of these issues in older chronic pain patients. The present study sought to examine the reliability and validity of the Pain Locus of Control (PLOC) scale when used with older patients, to explore age differences in PLOC orientation, and examine the relationship between cognitive beliefs and levels of pain and suffering. 169 older patients attending a pain management clinic completed a comprehensive psychometric battery prior to admission. Principal components analysis replicated the original factor structure of the PLOC previously identified in young adult samples, suggesting that older patients adopt the same underlying constructs of control. The internal item consistency of the 36 item scale was shown to be very good to excellent. Older adults endorsed a higher chance locus of control, but this orientation was amenable to change following a cognitive-behavioural treatment program. PLOC orientation was related to use of coping strategies, levels of pain and depression, functional and psychosocial impact as well as compliance with treatment protocols. Stepwise regression analysis revealed that self perceived interference from pain and internal PLOC were the best predictors of depressive symptoms in older adults. In combination, these findings suggest that cognitive factors are of importance in older chronic pain patients and extend the relevance of cognitive-behavioural models of pain across the entire adult age spectrum.

Skin vascular reactivity to the neuropeptide substance P in rats with peripheral mononeuropathy.

A compression neuropathy model that produces pain-related behaviour in rats was used to investigate changes in skin vascular reactivity in the innervated area. Neuropathy was produced by 4 ligatures tied loosely around the common sciatic nerve. Vascular reactivity was assessed via perfusion of the neuropeptide substance P (SP) over the base of a blister raised on the rat foot pad. Compared to sham-operated rats, experimental rats exhibited a decrease in their vasodilatation response to SP 2-5 weeks after ligatures were tied. A bilateral decrease in vasodilatation to sodium nitroprusside perfusion in treated rats suggested part of the altered SP response was due to diminished vascular reactivity. Plasma extravasation in response to SP was also decreased on the operated side of ligatured rats, significant 4 and 6 weeks after the operation. The results support studies that suggest neurogenic inflammation is altered in chronic neuropathic pain states.

The impact of dementia on the pain experience.

Advancing age is associated with an increased risk of illness. Investigating the influence of ageing on the experience of pain must take account of this association, as well as the impact of past experience of life. Dementia, which is almost exclusively restricted to older people, is an illness where the effects of past experience and future life anticipation are severely curtailed. The influence of dementia on the experience of pain has received little attention and many questions remain unanswered. This review draws upon this literature to describe current knowledge of the area. Suggestions for further research are made.

Free radicals contribute to the reduction in peripheral vascular responses and the maintenance of thermal hyperalgesia in rats with chronic constriction injury.

We previously reported that the time frame and the extent of the changes in the peripheral neurogenic inflammatory response in the skin area, innervated by an injured nerve, coincide with those of pain behaviours. We raised the possibility that common factors might operate to modulate neuropathic pain and peripheral neurogenic processes in rats with chronic constriction nerve injury (CCI). In the present study we examined the role of free radicals in modulating the neurogenic vascular response and thermal hyperalgesia in rats with CCI of the sciatic nerve. Free radicals, via an interaction with nitric oxide (NO) to form peroxynitrite, have previously been implicated in the maintenance of thermal hyperalgesia in CCI rats. In this study, we induced CCI of the sciatic nerve and the activity of xanthine oxidase (XO), which catalyzes the formation of superoxide anions, was measured in the injured nerve. In addition, we examined the effect of antioxidants on thermal hyperalgesia and on the neurogenic vascular response to substance P (SP) perfused over the base of a blister induced on the hind footpad skin which is innervated by the injured sciatic nerve. Compared with the sham operated group, CCI rats had a significantly higher XO activity in the injured sciatic nerve and significantly reduced thermal threshold and peripheral neurogenic vascular response to SP. Treatment with antioxidants, superoxide dismutase (SOD) or tirilazad significantly improved the neurogenic vascular response while tirilazad treatment significantly alleviated thermal hyperalgesia. The results therefore, suggest that free radicals are elevated in CCI animals and that they contribute to the maintenance of thermal hyperalgesia and the reduction in peripheral microvascular blood flow in the area innervated by the injured nerve. We raise the possibility that common mechanisms may govern the changes in neuropathic pain and in the peripheral neurogenic vascular responses in tissues innervated by the injured nerve.

Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers.

Recent animal studies using stress-induced analgesia have suggested a general age-related decline in endogenous pain inhibitory systems. The aim of the current study was to examine age-related differences in the magnitude of endogenous analgesia in human volunteers, using psychophysical measures of neuroselective electrical, and thermal CO(2) laser induced pain thresholds, before, immediately after and 1 h after repeated cold water immersion of the hand. Sensory detection thresholds did not differ between age groups indicating that the functional integrity of primary afferent sensory fibres appears to be intact in older people. Consistent with many previous studies, older adults required a higher intensity of noxious stimulation in order to first report the presence of pain. The cold water immersion task was effective in eliciting a powerful analgesic response, regardless of age; pain thresholds were shown to increase by up to 100% immediately after the cold pressor test. This effect was relatively transient with thresholds returning to baseline within 1 h. The magnitude of analgesic response, however, was found to be significantly less in older people. Age differences in the efficacy of endogenous analgesic systems may be expected to reduce the ability of older adults to cope with severe persistent pain states and may help explain some of the variation in the literature on pain report.

Cerebral event-related responses induced by CO2 laser stimulation in subjects suffering from cervico-brachial syndrome.

The present study was undertaken to examine possible changes in subjective appraisal and central nervous system processing, indexed by pain-related cerebral evoked potentials (N290, P400), of incoming noxious information in 20 pain-free control volunteers and 18 subjects suffering from right-side cervico-brachial pain (CBS). Detection threshold and cerebral evoked potentials were recorded in response to noxious CO2 laser stimulation of the right and left hands. The results indicate that when compared to controls, CBS subjects exhibit an elevation in detection threshold intensity and a reduction in the amplitude of the P400 peak following laser stimulation of the pain affected side. There were also differences in the choice of qualitative descriptor for laser stimuli although not in the subjective rating of stimulus intensity. These changes were not apparent for responses on the unaffected limb. The severity of clinical pain was found to be related to the magnitude of reduction in P400 amplitude only on the pain affected side. Conversely, feelings of anxiety were associated with higher amplitude responses on both the right and left sides, suggesting a more generalized relationship between these factors. We interpret these findings to indicate an alteration in central nervous system processing and subjective appraisal of acute experimental pain in subjects with chronic CBS. Moreover, these alterations appear to be restricted to pain affected pathways and are more related to the severity of clinical pain than to general mood state.

Capsaicin-induced flare and vasodilatation in patients with post-herpetic neuralgia.

The aim of the present study was to investigate the role of primary afferent fibres with polymodal nociceptors in the various pain symptoms and signs associated with post-herpetic neuralgia (PHN). Forty-four patients with PHN affecting thoracic dermatomes were examined clinically for evidence of sensory disturbance to touch and pinprick and compared to 14 normal subjects and 9 subjects with evidence of past herpes zoster infection but no pain. The patients were then divided into 3 groups on the basis of their clinical symptoms and signs-those with steady burning discomfort only (n = 12), those with burning discomfort, allodynia and hyperalgesia to pinprick (n = 17), and those with burning discomfort, allodynia and hypalgesia to pinprick (n = 15). Indirect measurement of primary afferent fibre function was performed by measuring the neurogenic axon reflex flare to topical capsaicin using Doppler flowmetry in the 5 clinical groups. The 2 groups with allodynia had significantly decreased neurogenic flare responses compared to PHN subjects without allodynia and the 2 control groups. These results suggest that allodynia in patients with post-herpetic neuralgia may be a consequence of disrupted function of primary afferent fibres.

The measurement of capsaicin-sensitive sensory nerve fiber function in elderly patients with pain.

The present study was undertaken to investigate the possible involvement of peripheral nociceptors in 3 diagnostic categories of elderly patients with chronic pain. The 3 diagnostic groups consisted of: chronic lower lumbar pain of degenerative musculoskeletal etiology (LLP), post-herpetic neuralgia (PHN) and pain of non-organic origin in a group with a predominantly psychiatric disorder (PPD). The last group had pain confined to the trunk. All patients documented subjective pain using a visual analogue scale and an 8-item pain descriptor scale. Topical application of capsaicin was used to induce an axon reflex flare in 25 patients with pain and 29 control subjects. Three forms of measurement were used: flare size measured by tracing and by laser Doppler flowmetry, latency to onset of increased skin blood flow and blood flux. The groups with LLP and PHN had reduced flares at the affected site by all 3 measures, whereas no decrease was observed in the PPD group. No significant difference was found between groups when tested on a control site remote from the affected area using the 3 forms of measurement. We suggest that an alteration in the function of capsaicin-sensitive sensory fibers could be related to the subjective report of subacute and chronic pain in diagnostic groups such as LLP and PHN where there is a known organic cause.

Widowhood and other demographic associations of pain in independent older people.

OBJECTIVES: To determine if psychosocial factors, as suggested by the demographic variables of widowhood and living alone, are associated with pain, particularly severe pain, in a representative sample of independent older people. DESIGN: One thousand older people (65+) randomly selected from independent residents living in a major city were surveyed about their health status (Health Status of Older People Study). Demographic characteristics, including age, gender, education, income, living alone, widowhood, and childlessness, were analyzed by logistic regression for their association with pain report of differing severity. Path analysis was used to confirm the association with pain severity and further define the role of mood disturbance in mediating this relationship. RESULTS: The prevalence of any pain report for the preceding 12 months was 56.3%. This was reduced when using more restrictive criteria, such that moderate-to-severe pain "at worst" and "at present" was found in 48.7% and 4.1% of the sample, respectively. After adjusting for type 1 error rate, the status of living alone was primarily associated with moderate-to-severe pain at worst, and being a widow(er) was associated with moderate-to-severe pain at present. The latter association had an estimated odds ratio greater than 3 and was characterized by more recent bereavement. Using path analysis, the model that severe pain was secondary to mood disturbance of widowhood, particularly recent bereavement, was tested and confirmed. The model explained 17% of the variance of pain severity in widow(er)s. CONCLUSION: The mood disturbance related to spousal bereavement aggravates pain in older people. This lends support to the biopsychosocial model of pain.

Dyskinetic patients show rebound worsening of affect after an acute L-dopa challenge.

BACKGROUND: Motor response complications that arise with repeated L-dopa administration for the treatment of Parkinson's disease are well understood but the relationship between motor response complications and affect are not. We proposed that patients with dyskinesias would report rebound worsening in affect during wearing-off of L-dopa effect. METHODS: Fifty Parkinson's disease patients with were assessed with the Purdue Pegboard test and rated Positive Affect and Negative Affect after overnight withdrawal of dopaminergic medications and half hourly for 6 h after a standard L-dopa challenge. Patients were carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. RESULTS: Positive Affect was improved by L-dopa in dyskinetics and to a lesser degree in fluctuators but not in stable responders. At T = 4-6 h, Positive Affect rebounded below baseline in dyskinetics only. On regression analysis, rebound worsening positively correlated with ratings of dyskinesia severity. Negative Affect improved with L-dopa in all groups and tended to remain below baseline for 6 h after L-dopa challenge. Peak effects of L-dopa on Positive Affect and Negative Affect occurred significantly earlier than effects on Purdue Pegboard test and were positively correlated with L-dopa equivalent daily dose. CONCLUSION: There is a clinical dissociation between L-dopa effects on motor function, Positive Affect and Negative Affect. Rebound worsening in Positive Affect occurred only in dyskinetic patients and the onset of rebound worsening occurred before the end of the motor benefit phase. These observations could explain why some Parkinson patients report wearing-off symptoms despite the external impression of good motor control.

Effect of electroacupuncture on opioid consumption in patients with chronic musculoskeletal pain: protocol of a randomised controlled trial.

BACKGROUND: Chronic musculoskeletal pain is common and has been increasingly managed by opioid medications, of which the long-term efficacy is unknown. Furthermore, there is evidence that long-term use of opioids is associated with reduced pain control, declining physical function and quality of life, and could hinder the goals of integrated pain management. Electroacupuncture (EA) has been shown to be effective in reducing postoperative opioid consumption. Limited evidence suggests that acupuncture could assist patients with chronic pain to reduce their requirements for opioids.The proposed research aims to assess if EA is an effective adjunct therapy to standard pain and medication management in reducing opioids use by patients with chronic musculoskeletal pain. METHODS: In this multicentre, randomised, sham-acupuncture controlled, three-arm clinical trial, 316 patients regularly taking opioids for pain control and meeting the defined selection criteria will be recruited from pain management centres and clinics of primary care providers in Victoria, Australia. After a four-week run-in period, the participants are randomly assigned to one of three treatment groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants receive routine pain medication management delivered and supervised by the trial medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are delivered over 10 weeks. Upon completion of the acupuncture treatment period, there is a 12-week follow-up. In total, participants are involved in the trial for 26 weeks. Outcome measures of opioid and non-opioid medication consumption, pain scores and opioid-related adverse events are documented throughout the study. Quality of life, depression, function, and attitude to pain medications are also assessed. DISCUSSION: This randomised controlled trial will determine whether EA is of significant clinical value in assisting the management of debilitating chronic pain by reducing opioids consumption and their associated adverse events, as well as improving the quality of life for those with chronic pain. Such an outcome will provide the rationale for including EA into multidisciplinary programmes for effective management of chronic musculoskeletal pain. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12609000676213)http://www.anzctr.org.au/trial_view.aspx?ID=308008.

The effect of local anaesthetic on age-related capsaicin-induced mechanical hyperalgesia--a randomised, controlled study.

Adults over 65 years exhibit a prolonged punctate hyperalgesia induced by topical application of capsaicin. The aim of this study was to investigate the role of peripheral afferent input in the slowed resolution of punctate hyperalgesia in older people. Twenty young (25.7+/-4.8 years) and 19 old (74.9+/-4.4 years) healthy adults were recruited, and subjects in each age group were randomly assigned to receive either EMLA cream (a local anaesthetic) (n=10 in each age group) or Sorbolene treatment (n=9 in the older group, n=10 in the young group) after the development of punctate hyperalgesia. EMLA cream blocked punctate sensation and greatly reduced touch and warmth sensation. In comparison to Sorbolene treatment, EMLA abolished stroking but not punctate hyperalgesia in both age groups. The area of punctate hyperalgesia was maintained in older adults over 4 h, while it declined in the young. Older adults also reported reduced ratings to capsaicin-induced sensation and to stroking stimulation, and had a smaller area of stroking hyperalgesia. Ratings to punctate stimulation did not, however, differ between the age groups. Stoicism and cautiousness measured with Pain Attitude Questionnaire were negatively correlated with highest pain rating in the young, but not in the older groups. We suggest that the prolonged punctate hyperalgesia in older adults is possibly sustained by central mechanisms, indicating age differences in central plasticity following acute injury. The relationship between such age-related changes and the chronicity of pain in older adults should be further explored.

The effect of electroacupuncture on opioid-like medication consumption by chronic pain patients: a pilot randomized controlled clinical trial.

Opioid-like medications (OLM) are commonly used by patients with various types of chronic pain, but their long-term benefit is questionable. Electroacupuncture (EA) has been previously shown beneficial in reducing post-operative acute OLM consumption. In this pilot randomized controlled trial, the effect of EA on OLM usage and associated side effects in chronic pain patients was evaluated. After a two-week baseline assessment, participants using OLM for their non-malignant chronic pain were randomly assigned to receive either real EA (REA, n=17) or sham EA (SEA, n=18) treatment twice weekly for 6 weeks before entering a 12-week follow-up. Pain, OLM consumption and their side effects were recorded daily. Participants also completed the McGill Pain Questionnaire (MPQ), SF-36 and Beck Depression Inventory (BDI) at baseline, and at the 5th, 8th, 12th, 16th and 20th week. Nine participants withdrew during the treatment period with another three during the follow-up period. Intention to treat analysis was applied. At the end of treatment period, reductions of OLM consumption in REA and SEA were 39% and 25%, respectively (p=0.056), but this effect did not last more than 8 weeks after treatment. There was no difference between the two groups with respect to reduction of side effects and pain and the improvement of depression and quality of life. In conclusion, REA demonstrates promising short-term reduction of OLM for participants with chronic non-malignant pain, but such effect needs to be confirmed by trials with adequate sample sizes.

The prevention and management of herpes zoster.

The burden of illness from herpes zoster (HZ) and postherpetic neuralgia (PHN) in the Australian community is high. The incidence and severity of HZ and PHN increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). Antiviral medications (valaciclovir, famciclovir, aciclovir) have been shown to be effective in reducing much but not all of the morbidity associated with HZ and PHN, but are consistently underprescribed in Australia. Zoster-associated pain should be treated early and aggressively, as it is more difficult to treat once established. Clinicians should be proactive in their follow-up of individuals at high risk of developing PHN, and refer patients to a specialist pain clinic earlier, rather than later. A live, attenuated VZV vaccine (Oka/Merck strain, Zostavax [Merck Sharp & Dohme]) has proven to be efficacious in reducing the incidence of and morbidity associated with HZ and PHN in older adults. The vaccine's efficacy has been shown to persist for at least 4 years, but is likely to last a lot longer. Ongoing surveillance will determine the duration of protection and whether a booster dose is required. Clinicians should consider recommending the vaccine, which can be safely administered at the same time as the inactivated influenza vaccine, to all immunocompetent patients aged 60 years or older. Clinicians should refer to the Australian immunisation handbook for advice on the use of the live vaccine in immunosuppressed individuals.