Summaries

The Journal of Pain

Highlights from The Journal of Pain (Volume 17, No. 7, July 2016 Issue)

Distress Intolerance Associated with Opioid Misuse

R. Kathryn McHugh, Roger D. Weiss, Marise Cornelius, Marc O. Martel, Robert N. Jamison, Robert R. Edwards; Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA; Pain Management Center, Brigham and Women’s Hospital, Chestnut Hill, MA; Department of Psychiatry, Harvard Medical School, Boston, MA

Inability to manage negative emotional and somatic stress is associated with opioid misuse in adults with chronic pain, according to a new study reported in The Journal of Pain.

Researchers from Harvard Medical School, Brigham and Women’s Hospital, and McLean Hospital investigated if high distress intolerance would make patients with chronic pain more likely to misuse opioid analgesics. Previous research suggests those with chronic pain who misuse their opioids exhibit higher levels of distress in general, as well as heightened reactivity to that distress.

Distress intolerance is defined as the perceived or actual inability to cope with adverse somatic or emotional stress. This condition can be treated effectively with cognitive behavioral therapy. For their study, the authors hypothesized that participants with higher distress intolerance levels would be more likely to misuse their prescribed opioids. They also examined if stress intolerance was associated with high pain sensitivity.

The study evaluated 51 participants from the pain management clinic at McLean Hospital in Belmont, MA. Subjects completed questionnaires and self-reports probing for pain severity, pain thresholds, distress intolerance, and opioid misuse.

Results showed that self-reported distress intolerance was significantly associated with opioid misuse in the study sample. For every one-unit increase in the Distress Intolerance Index, the likelihood of being in the opioid misuse group was 12% higher. Of the 51 study subjects, 31 met criteria for opioid misuse.

Distress intolerance was not associated with greater pain sensitivity, but was linked with higher pain-related anxiety. The authors noted that distress is targeted extensively in cognitive behavioral therapy and can be modified with treatment.

Study Shows Ways to Improve Pain Intensity in Older Veterans

Steven K. Dobscha, Travis I. Lovejoy, Benjamin J. Morasco, Anne E. Kovas, Dawn M. Peters, Kyle Hart, J. Lucas Williams, Bentson H. McFarland; Center to Improve Veteran Involvement in Care, Veterans Affairs Portland Health Care System, Portland, OR; Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR; Department of Psychiatry, Oregon Health and Science University, Portland, OR

Older military veterans frequently show improvements in pain intensity over time. However, opioids, some mental health conditions, and certain pain diagnoses are associated with lower likelihood for improvement, according to research reported in The Journal of Pain.

The aging veteran population is at especially high risk for persistent pain. Unfortunately, little is known about factors linked with positive and negative outcomes over time. Further, older adults have the highest prevalence of long-term use of pain medications, including opioids.

Researchers at the Center to Improve Veterans Involvement in Care and Oregon Health and Science University sought to identify clinical and demographic factors associated with changes in pain scores over time in a national cohort of veterans 65 years and older with indications of chronic pain. They hypothesized that older age and comorbid mental health disorders would be associated with less improvement in pain conditions over time.

The study examined a database of approximately 13,000 veterans receiving treatment in the VA system who had elevated numeric rating pain scores and had not been prescribed opioids. Researchers measured the percentage decrease over 12 months in average pain intensity scores and the time to sustained improvement.

Results showed that nearly two-thirds of these patients met criteria for sustained improvement during the 12-month follow-up period. A key finding was that initiation of opioid therapy was associated with lower likelihood for sustained improvement. Other factors associated with poor improvement were service-connected disability and mental health problems, chronic low back pain, neuropathy, and fibromyalgia/myofascial pain diagnoses.

The authors reported that clinically significant improvements in pain intensity scores in two-thirds of the study sample could indicate that pain treatments are effective in helping move high pain intensity scores to moderate or low ratings, and that many older people with pain adjust and cope better over time.

Although two-thirds of the sample experienced pain improvement over time, a substantial minority of veterans did not show reductions in pain intensity and some had exacerbated pain.

The authors concluded their findings call for further evaluation of pain outcomes in older adults and, in particular, there is a need for more research to study the relationship between prescription opioids and treatment outcomes over time.

PAIN

Highlights from PAIN (Volume 157, No. 7, July 2016 Issue)

A Randomized Controlled Trial of Gabapentin for Chronic Low Back Pain with and Without a Radiating Component

J. Hampton Atkinson, Mark A. Slater, Edmund V. Capparelli, Shetal M. Patel, Tanya Wolfson, Anthony Gamst, Ian S. Abramson, Mark S. Wallace, Stephen D. Funk, Thomas R. Rutledge, Julie L. Wetherell, Scott C. Matthews, Sidney Zisook, Steven R. Garfin, VA San Diego Healthcare System, San Diego, CA; Department of Psychiatry, University of California, San Diego, La Jolla, CA; Scottsdale Healthcare Research Institute, Scottsdale, AZ; Department of Pediatrics, University of California, San Diego, La Jolla, CA; Computational and Applied Statistics Laboratory, University of California, San Diego, La Jolla, CA; Departments of Mathematics, Anesthesiology, and Orthopaedic Surgery, University of California, San Diego, La Jolla, CA

This study’s investigators conducted a 12-week, two-arm, randomized, double-blind, placebo-controlled trial to examine the efficacy of gabapentin for patients with chronic low back pain with or without leg pain. They recruited patients from primary care and community settings (rather than pain specialty centers) to enhance generalizability. A 12-week design was used to guard against a trend toward analgesic efficacy associated with brief trials. This randomized, two-arm, parallel group study compared gabapentin (forced titration up to 3,600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment as measured by the Descriptor Differential Scale; the secondary outcome was disability (as measured by the Oswestry Disability Index).

This randomized phase 2 clinical trial on chronic nonspecific low back pain did not detect analgesic effects for gabapentin compared with placebo. Adverse effects were higher than expected, considering that gabapentin often is regarded as having a benign side effect profile. In light of evidence showing that gabapentin is efficacious for neuropathic pain syndromes, investigators also examined whether back pain with a radiating component into the legs was differentially responsive. Again, there was no support for gabapentin analgesia. The secondary outcome of disability in everyday function attributable to back pain also indicated no difference between gabapentin and placebo. Reasons for this lack of effect are not clear, but they may be related to the etiopathogenesis of back pain, characteristics of the back pain sample, dosing or plasma concentration, or methodological limitations of the research.

The calcium channel alpha 2–delta ligand gabapentin, which is analgesic for selected neuropathic pain conditions and widespread pain disorders (fibromyalgia), was expected to be effective for chronic back pain, considering its overlap with both neuropathic and diffuse musculoskeletal pain syndromes. Results did not support its use in a general low back pain sample with or without pain radiating to the legs. Future studies using larger chronic back pain samples selected to assess neurologic syndromes such as sciatica may help to define a therapeutic role for gabapentin.

Combination of Pregabalin with Duloxetine for Fibromyalgia: A Randomized Controlled Trial

Ian Gilron, Luis E. Chaparro, Dongsheng Tu, Ronald R. Holden, Roumen Milev, Tanveer Towheed, Deborah DuMerton-Shore, Sarah Walker; Departments of Anesthesiology and Perioperative Medicine and Biomedical and Molecular Sciences, Queen’s University, Kingston, Canada; Department of Anesthesia, University of Toronto, Toronto, Canada; Public Health Sciences, Mathematics and Statistics, Psychology and Psychiatry, Queen’s University, Kingston, Canada; Division of Rheumatology, Department of Medicine, Queen’s University, Kingston, Canada; Department of Anesthesiology and Perioperative Medicine, Queen’s University, Kingston, Canada

Varying levels of evidence support a diverse array of treatments for fibromyalgia, including exercise; medications; and physical, psychological, and other therapies. In particular, the anticonvulsant pregabalin and the antidepressant duloxetine are two newer pharmacological therapies that are widely used and have received regulatory approval in several countries for the treatment of fibromyalgia. Pregabalin and duloxetine are thought to reduce pain by different pharmacological actions. Pooled evidence from multiple trials of these drugs as monotherapies suggests only partial benefit for most patients because of incomplete efficacy or intolerable side effects at higher doses. This trial compares a pregabalin-duloxetine combination to each monotherapy for the management of fibromyalgia. Using a randomized, double-blind, four-period crossover design, participants received maximally tolerated doses of placebo, pregabalin, duloxetine, and a pregabalin-duloxetine combination for 6 weeks.

For the primary outcome of pain intensity, results demonstrated superiority of a pregabalin-duloxetine combination to pregabalin monotherapy; however, trends favoring combination over duloxetine monotherapy failed to reach significance. Although the combination was not statistically superior to duloxetine for the primary outcome, this trial demonstrated substantial and statistically significant superiority of combination to duloxetine monotherapy (as well as pregabalin) for global pain relief, functional improvement (Fibromyalgia Impact Questionnaire), and overall quality of life (SF-36 Health Survey) as well as for total scores of the Short-Form McGill Pain Questionnaire. Although drowsiness was more frequent with the combination (versus duloxetine alone), safety assessments conducted in this clinical trial cohort suggest that the pregabalin-duloxetine combination demonstrated a somewhat comparable tolerability profile versus either monotherapy.

These results suggest that combining pregabalin with duloxetine can safely improve outcomes in fibromyalgia, including pain relief, physical function, and overall quality of life. These benefits may come with risk for increased drowsiness. Studies of different drug combinations that are currently used in practice with limited supportive evidence would be useful. Future analgesic trials that concurrently evaluate physical activity and pain may help clarify the complex interactions between analgesia, adverse effects, and physical function.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 32, No. 7, July 2016 Issue)

Characterization of Migraineurs Having Allodynia Results of a Large Population-Based Study

Betul Baykan, Esme Ekizoglu, Necdet Karlı, Elif Kocasoy-Orhan, Mehmet Zarifoglu, Sabahattin Saip, Aksel Siva, Mustafa Ertas; Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey; Department of Neurology, Faculty of Medicine, Uludag University, Bursa, Turkey

Allodynia, pain resulting from application of a nonnoxious stimulus to healthy skin, is a well-described symptom of migraine. This nonspecific phenomenon has been reported in relation to other primary headaches and some secondary headache disorders. Manifestations of allodynia include discomfort when combing the hair; shaving; and wearing glasses, contact lenses, earrings, a hat, or tight clothing. The importance of allodynia in clinical practice is often overlooked, and some of its clinical associations are underrecognized as a missing link. It also is not known if some people have a higher inherited propensity for developing allodynia than others. These investigators studied the prevalence of allodynia and its unknown clinical associations using a population-based study design to better understand mechanisms and usefulness in migraine management. They designed a nationwide, home-based prevalence study for adults, with face-to-face interviews by 33 specially trained general physicians using a structured electronic questionnaire.

In the study population, disease duration was significantly longer in patients with migraine with allodynia than those without allodynia, but the frequency of attacks was 6.2 ± 6.4 per month, which was not different in allodynic migraineurs in comparison with 5.5 ± 5.2 per month in migraineurs without allodynia (p > .05). The allodynia rate was 70.5% for patients having migraine with aura. Experiencing many different types of aura correlates with the presence of allodynia in migraineurs.

Allodynia was found more frequently (61.1%) in patients with definite migraine. Female sex, family history of migraine, and the presence of multiple aura types were significantly associated with the presence of allodynia, whereas demographic variables such as income or education were not issues among migraineurs with this phenomenon. The presence of multiple aura types in allodynic migraineurs and the link between allodynia and family history of headache supported the involvement of genetic factors in the development of allodynia. There also was an association between the presence of allodynia and osmophobia in patients having migraine. Patients with allodynia are more sensitive to endogenous estrogen changes (there is a higher tendency for migraine attacks during menstrual periods and with oral contraceptive use) than patients without allodynia, which may be related to the genetic diversity of this group.

Many migraine-related symptoms, including premonitory signs, are associated with allodynia, and all of these symptoms seem to result from a genetically hyperexcitable central nervous system. Allodynia appears to be related to the headache chronification and the tendency for headache attributable to medication overuse. Clinical allodynia should be investigated carefully and in daily headache practice to help predict prognosis and determine treatment strategies.

Influence of Therapeutic Approach in the TENS-Induced Hypoalgesia

Mayara E. d. J. Agripino, Lucas V. Lima, Ingrid F. Freitas, Natália B. R. Souto, Taís C. S. Carvalho, Josimari M. DeSantana; Department of Physical Therapy, Graduate Programs in Health Science and Physiology, Federal University of Sergipe, Aracaju, Sergipe, Brazil

Transcutaneous electrical nerve stimulation (TENS) is a noninvasive, nonpharmacological, and low-cost analgesic resource defined by the American Physical Therapy Association as an application of electrical stimulation to the skin for pain control. Besides producing a significant reduction in pain intensity, TENS also promotes a reduction in analgesic consumption. The impacts of patient expectations have been poorly studied in some modalities used by physical therapists (PTs), such as manual therapy, acupuncture, and massage therapy. This study was designed to determine how a therapist’s approach regarding the effects of TENS intervention can influence the hypoalgesia promoted by this form of electrostimulation.

Pain-free participants (161) had their demographics, perceived pain intensity, pressure pain threshold (PPT), anxiety level, and State-Trait Anxiety Inventory score measured. They were then randomly assigned into six study groups: three active and three placebo TENS associated with positive, negative, or neutral approaches about electrical stimulation, as given by the investigator. After the treatment, all parameters were reassessed.

PPT was assessed through a digital pressure algometer. Participants were instructed to say “stop” when the pressure sensation became clearly painful, and the pressure value was recorded. A numerical scale was used to measure perceived pain during the PPT assessment before and after the TENS intervention. Active TENS-treated participants receiving either positive or neutral expectations showed a significant increase in PPT (p < .02). However, there was no significant difference in the group treated with active TENS and negative expectation when compared with pretreatment in both the anatomic snuffbox and forearm region. None of the placebo TENS-treated groups showed a statistical difference between the posttreatment and pretreatment moments.

Expectations generated by the PT can positively or negatively influence the analgesic effect promoted by TENS. In this study, negative expectations promoted unfavorable outcomes regarding the analgesic properties of TENS; however, the positive and neutral expectations proved to be favorable to the analgesic effects produced by the current. These authors contend the approach taken by the PT should be used to convey positive expectations.