Efficacy and Safety of Low Dose Naltrexone for Chronic Pain.

Naltrexone is a mu-opioid receptor antagonist increasingly used as an analgesic for chronic pain at low doses. This retrospective, observational cohort study was conducted at an academic medical center to evaluate low-dose naltrexone (LDN) efficacy and describe its use in routine clinical practice. Adults receiving LDN, doses <10 mg for ≥1 month, seen at an outpatient pain clinic from January 1, 2014 to April 1, 2022 were included. The primary outcome was change in the Pain, Enjoyment of Life, and General Activity (PEG) score after LDN. Thirty-one patients were included. Median age was 50 years and 71% were female. Median duration of pain at baseline was 5 years. Mean PEG scores were 7.27 ± 1.39 and 6.62 ± 2.04 at baseline and follow-up, respectively. Mean difference was 0.66 (95% CI [0.10-1.21], p = 0.022). Eighty-seven percent (27) of patients discontinued LDN, 52% (16) for lack of benefit, 23% (7) for loss of benefit, 10% (3) for side effects, and 3% (1) for other reasons. Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.

When opioids fail in chronic pain management: the role for buprenorphine and hospitalization.

Clinicians are increasingly being challenged by patients who are treated for chronic pain with high-dose opioids that can cause medical, social, and societal harm. These patients may best be improved by psychological approaches, adjuvant medications, and opioid reduction or removal, rather than ever-escalating dosing that has become common. Opioid reduction or removal can be a difficult process that, when done incorrectly, may cause patient dissatisfaction or severe discomfort. Buprenorphine, a partial opioid agonist, is slowly becoming recognized as an effective pain treatment, possessing a wide safety margin while offering the opportunity for stabilization of opioid dosing or even removal. We have developed a protocol for hospitalization of the most fragile or toxic patients detailed herein that can permit a comfortable conversion to buprenorphine from prior high-dose full agonist opioid therapy. Seventy-six consecutive patients with serious medical, psychological, or addiction comorbidities, treated with morphine equivalent doses exceeding hundreds of milligrams per day, were followed after conversion for up to 25 months. Two-thirds reported moderate to dramatic improvements of pain and functional status with an increase seen in employment. Median length of hospital stay was 2 days, and the median daily buprenorphine discharge dose was 8 mg. No adverse reactions or outcomes were observed. A brief hospitalization for conversion from high-dose opioid therapy to a safer, more effective buprenorphine regimen can produce life-altering improvement.

Rational use of opioids for management of chronic nonterminal pain.

Opioid prescribing for chronic nonterminal pain has increased in recent years, although evidence for its long-term effectiveness is weak and its potential for harm is significant. Nonmedical use of prescription opioids, diversion, and overdose deaths have also increased sharply, sparking concern about the safety of these medications. Physicians considering initiation or continuation of opioid therapy for a patient with chronic nonterminal pain should first use a structured approach that includes a biopsychosocial evaluation and a treatment plan that encourages patients to set and reach functional goals. There should be a comprehensive evaluation for the cause of pain, assessment for risk of opioid complications (including misuse and addiction), and a detailed treatment history, including a review of medical records and data from the state prescription monitoring program. Opioids should be prescribed on a trial basis, to be continued only if progress toward functional goals is demonstrated. Long-acting morphine is the preferred initial drug, although several alternatives are available. Ongoing monitoring for safety and effectiveness is essential, including regular review of functional progress or maintenance, urine drug testing, and surveillance of data from the state prescription monitoring program. Ineffective, unsafe, or diverted opioid therapy should be promptly tapered or stopped.

Comparative Effectiveness of Treatments for Chronic Low Back Pain: A Multiple Treatment Comparison Analysis.

STUDY DESIGN: A systematic review and network meta-analysis. OBJECTIVE: To determine current treatment options of chronic low back pain (LBP) as defined by randomized controlled trials (RCTs) and to compare effectiveness of those treatments using a mixed-treatment comparison (MTC). SUMMARY OF BACKGROUND DATA: It is important to provide an evidence-based assessment of the treatment options that exist for LBP. METHODS: A systematic search of RCTs was conducted in MEDLINE and the Cochrane Collaboration Library from 1990 to 2014. From the selected studies, we extracted preoperative and postoperative ODI and VAS back pain scores, additional surgeries, and complications. Standard and network meta-analytic techniques were used. RESULTS: Twelve RCTs were included in the analysis: 5 total disk replacement (TDR) versus fusion; 1 TDR versus exercise and cognitive behavioral therapy (CBT); 5 fusion versus exercise and CBT; and 1 fusion versus physical therapy (PT). On the basis of MTC, with respect to ODI change scores, the pooled mean difference favoring fusion over exercise and CBT was 2.0 points (95% CI, -1.2 to 4.8). The pooled mean difference favoring TDR over exercise and CBT was 6.4 points (95% CI, 3.2-9.3). The pooled mean difference favoring fusion over PT was 8.8 points (95% CI, 4.1-13.6). The pooled mean differences favoring TDR over fusion was 4.4 points (95% CI, 2.37-6.63). For PT versus structured exercise with CBT, the pooled mean difference favoring exercise with CBT over PT was 6.8 points (95% CI, 1.5-12.8). For TDR versus PT, the pooled mean difference favoring TDR over PT was 13.2 points (95% CI, 8.0-18.4). Additional surgery rates were similar between treatment options. CONCLUSIONS: All 4 treatments provided some benefit to patients with chronic LBP. According to the MTC analysis, TDR may be the most effective treatment and PT the least effective treatment for chronic LBP. This review is based on a limited number of RCT studies and does not support any 1 treatment modality for all patients.

Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists.

OBJECTIVES: To assess changes in phenotype and pressure sensitivity in patients with suspected opioid-induced-hyperalgesia (OIH) after transitioning to buprenorphine. METHODS: Twenty patients with suspected OIH were enrolled to transition to buprenorphine therapy. Patients completed validated self-report measures at baseline and at 1, 4, 8 weeks, and 6 months after initiation of buprenorphine along with quantitative sensory testing including measures of pressure pain threshold, pain tolerance and Pain 50 (a pain intensity rating). RESULTS: 20 patients were enrolled, 17 were treated with buprenorphine and 11 completed all assessment points. We found that after transitioning to buprenorphine, patients on higher opioid doses (≥100mg oral morphine equivalents) had significant improvements for some measures including decreased pain severity and fibromyalgia survey scores, fewer neuropathic pain features, less catastrophizing, fewer depressive symptoms, and improved functioning 1-week after transitioning to buprenorphine with an eventual return back to baseline. Although not statistically significant, patients on high dose opioids (≥100mg OME) also showed a trend of decreased pressure sensitivity 1-week after transitioning to buprenorphine with a gradual return back to baseline. CONCLUSIONS: Our study is the first to look at pressure pain sensitivity in patients who were taking opioids and transitioned to buprenorphine. These results suggest that the patients most likely to benefit from buprenorphine therapy are those on higher doses. In addition, the eventual return back to baseline on measures of pain phenotype and pressure sensitivity suggests that buprenorphine may over time result in a return of the hyperalgesic effects of a full mu agonist.

Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia.

BACKGROUND AND OBJECTIVES: This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia (OIH). METHODS: Twenty patients on long-term opioid therapy with suspected OIH were recruited along with 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels were evaluated. As a secondary outcome, changes in pressure pain sensitivity after intravenous administration of placebo (saline) and fentanyl (1.5 µg/kg) were assessed. RESULTS: There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r = -0.46, P = 0.041) and lower Pain50 (r = -0.46, P = 0.044), which was consistent with the hypothesis. Patients on more than 100 mg oral morphine equivalents displayed decreased pressure pain tolerance compared with patients taking less than 100 mg oral morphine equivalents (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P = 0.002). CONCLUSIONS: Whereas there were no differences between patients suspected of having OIH and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.

Relationship between health insurance and medical care for patients hospitalized with human immunodeficiency virus-related Pneumocystis carinii pneumonia, 1995-1997: Medicaid, bronchoscopy, and survival.

In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients.

Dexmedetomidine as a novel therapeutic for postoperative pain in a patient treated with buprenorphine.

Buprenorphine is a partial agonist/antagonist used for the outpatient management of pain and addiction. It avidly binds to the opioid receptors and has a long and varied half-life. Its effects can impair the efficacy of opioids used for postoperative pain. The authors present a case of a patient managed with buprenorphine as an outpatient who presented for revision spine surgery and had significant postoperative pain that was successfully treated with hydromorphone and dexmedetomidine. This is the first reported use of dexmedetomidine for postoperative pain in a patient treated with buprenorphine.