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Effect of gastroretentive gabapentin (Gralise) on postmastectomy pain syndrome: a proof-of-principle open-label study

imageIntroduction:
Chronic pain is a common and debilitating complication following breast surgery. One of the most challenging for treatment is the neuropathic pain condition, postmastectomy pain syndrome (PMPS). Gabapentin is a pharmacotherapy for neuropathic pain disorders; however, its once-daily, gastroretentive formulation, Gralise, has not been evaluated in PMPS.
Objective:
To evaluate the safety and effectiveness of Gralise in patients with moderate-to-severe PMPS.
Methods:
The primary effectiveness endpoint was a change in the worst pain intensity score from baseline to completion of 8 weeks of Gralise therapy. The secondary endpoints included the change in mood, coping behavior, sleep, and function. Sensitivity to experimental stimuli was tested before and after treatment via quantitative sensory testing. The incidence and type of adverse event were used to evaluate the safety and tolerability of Gralise.
Results:
Twenty-one patients with confirmed moderate-to-severe PMPS were enrolled. Nineteen of 21 (90.5%) patients completed the 8-week treatment with Gralise. A significant positive change was found in pain intensity, pain impact, and sleep. There was no change in sensory testing scores. Of total, 63.16% of patients reported reduction in present pain, 78.95% in average pain, 89.47% in worst pain, and 84.21% in overall pain severity at posttreatment visit. No significant adverse effects were noted in the study.
Limitations:
Variation in type of breast surgery, small sample size, lack of placebo control.
Conclusion:
There was a significant improvement in pain and sleep, and Gralise was well tolerated in patients with PMPS. Further investigation is warranted.

Effect of gastroretentive gabapentin (Gralise) on postmastectomy pain syndrome: a proof-of-principle open-label study


Orginally Published At: PAIN Reports

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The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents

imageIntroduction:
A marked rise in opioid prescriptions for patients with chronic noncancer pain (CNCP) with a parallel increase in opioid abuse/misuse, and resulting deaths was noted in the Unites states in the past decade (opioid epidemic). In response, the US Center of Diseases Control (CDC) developed a guideline for prescribing of opioids for patients with CNCP.
Objectives:
To assess (1) if there is an opioid epidemic in Australia, Canada, and Germany (2) to compare Australian, Canadian, German, and Center of Diseases Control guidelines recommendations for long-term opioid therapy for CNCP.
Methods:
National evidence-based guidelines and PubMed were searched for recommendations for opioid prescriptions for CNCP.
Results:
There are signs of an opioid epidemic in Australia and Canada, but not in Germany. Guidelines in all 4 countries provide similar recommendations: opioids are not the first-line therapy for patients with CNCP; regular clinical assessments of benefits and harms are necessary; excessive doses should be avoided (recommended morphine equivalent daily doses range from 50 to 200 mg/d); stopping rules should be followed. All guidelines do not recommend the use of opioids in chronic pain conditions without an established nociceptive or neuropathic cause such as fibromyalgia and primary headache.
Conclusion:
Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents


Orginally Published At: PAIN Reports

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The impact of pain-related fear on neural pathways of pain modulation in chronic low back pain

imageIntroduction:
Pain-related fear plays a substantial role in chronic low back pain (LBP) by amplifying the experienced disability. Related dysfunctional emotions and cognitions may also affect sensory aspects of pain through a modulatory pathway in which the periaqueductal gray (PAG) and the amygdala play key roles.
Objectives:
We therefore hypothesized a differential amygdala-PAG functional connectivity (FC) in patients with chronic LBP that is modulated by the degree of pain-related fear.
Methods:
We used data of a previously reported fMRI study where 20 chronic LBP patients (7 females, mean age = 39.35) and 20 healthy controls (12 females, mean age = 32.10) were asked to observe video clips showing potentially harmful and neutral activities for the back. Pain-related fear was assessed using the Tampa Scale of kinesiophobia (TSK) and Fear Avoidance Beliefs questionnaires (FABQ). Generalized psychophysiological interactions were used to reveal task-based FC.
Results:
Compared to controls, patients exhibited a significant decrease in amygdala-PAG-FC (P = 0.022) during observation of harmful activities, but not of neutral activities. Furthermore, amygdala-PAG-FC correlated negatively with Tampa Scale of kinesiophobia scores in patients (R2 = 0.28, P = 0.01) but not with Fear Avoidance Beliefs questionnaires scores.
Discussion:
Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.

The impact of pain-related fear on neural pathways of pain modulation in chronic low back pain


Orginally Published At: PAIN Reports

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Nocebo effects in clinical studies: hints for pain therapy

imageIntroduction:
Nocebo-induced algesic responses occurring within clinical contexts present a challenge for health care practitioners working in the field of pain medicine.
Objectives:
Following the recent research on algesic nocebo effects, the scope of this review is to develop ethically acceptable strategies to help avoid, or at least reduce, nocebo responses within clinical settings.
Methods:
We reviewed relevant clinical studies that depict how patient-practitioner interactions may contribute to the reduction of nocebo responses.
Results:
A strong algesic nocebo effect may adversely impact a patient’s condition by causing decreases in both the efficacy and effectiveness of interventions, as well as by promoting treatment nonadherence and discontinuation. These effects may be triggered through multiple channels and can lead to significant alterations in a patient’s perception of pain, consequently producing a weakening of the specific positive effects of pharmacological, psychological, or physical pain-management interventions.
Conclusion:
To minimize nocebo effects in clinical settings, we identified and discussed five contextual aspects relevant to the treatment of patients with chronic pain: (1) negative patient–clinician communication and interaction during treatment; (2) emotional burden of patients during treatment with analgesic medication; (3) negative information provided via informational leaflets; (4) cued and contextual conditioning nocebo effects; and (5) patient’s lack of positive information. Through an understanding of these elements, many preventive and ethically acceptable clinical actions can be taken to improve multidisciplinary pain treatment outcomes.

Nocebo effects in clinical studies: hints for pain therapy


Orginally Published At: PAIN Reports

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Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice

imageIntroduction:
Suboptimal management of postoperative pain leads to increased risk of chronic opioid therapy, especially in elderly patients.
Objectives:
Although this age-dependent phenomenon has been observed clinically, basic mechanisms including baseline nociception, postoperative hypersensitivity, and mu-opioid efficiency in aged animals have never been evaluated.
Methods:
We tested these criteria using incision model on adult (3–6 months) and aged (24 months) mice to assess translatability of postoperative animal studies to clinical observations.
Results:
Thermal and mechanical testing revealed lower baseline nociception in aged vs adult mice, while behavioral assays after hind paw plantar incision showed similar hypersensitivity levels for both age groups. Efficiency of local and spinal mu-opioid injections on postoperative pain was assessed next. DAMGO, a pure mu-opioid, was effective in reducing postoperative hypersensitivity in aged and adult mice, although adult mice displayed increased sensitivity to higher doses (50 μg local; 1–15 μg spinal). Buprenorphine, a mixed mu-opioid agonist, produced dose-dependent antihypersensitivity with adult mice more sensitive to lower doses (0.1 μg local; 0.02 μg spinal), and aged mice more sensitive to higher doses (1, 10 μg local; 0.1, 1 μg spinal). Finally, exploratory locomotor activity was used to evaluate the suppression of incision-induced spontaneous pain by DAMGO. Spinal and systemic (intraperitoneal) DAMGO inhibited ongoing pain more in adults compared with aged mice.
Conclusion:
As in humans, baseline nociception was lower in aged vs adult mice, while postoperative hypersensitivity magnitudes were comparable between groups. Unlike in humans, adult mice were more sensitive to mu-opioids, although higher doses of mixed mu-opioids were more effective for postoperative antihypersensitivity in aged mice.

Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice


Orginally Published At: PAIN Reports