Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists.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

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.

Sublingual buprenorphine is effective in the treatment of chronic pain syndrome.

Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.