Long-term use of opioids for complex chronic pain
Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription-opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. Although short-term randomised trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain remains unknown. Given the lack of large, long-term randomised trials, recent epidemiologic data suggest the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed.
Available from: Tianle Gao
- "The first line drugs used to treat neuropathic pain, such as pregabalin or gabapentin, only produce partial pain relief in a subset of patients   . Opioid analgesics are ineffective against neuropathic pain in the majority of patients and are often associated with side effects including constipation, tolerance and drug abuse  . Traditional Chinese medicines (TCM) are widely used for management of various clinical pain conditions in China and may harbour a rich source of potential drug candidates, which Western drug companies are turning to with ever increasing urgency . "
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ABSTRACT: Background and aims
We have previously reported that systemic administration of sinomenine produced antinociception in various experimental pain conditions in rodents, particularly in models of neuropathic pain. In the present study we assessed the effects of repeated administration of sinomenine in two rodent models of neuropathic pain in order to study the development of tolerance.
The analgesic effect of sinomenine was tested in female Sprague-Dawley rats that exhibited mechanical and cold hypersensitivity following ischaemic injury to the spinal cord and in male C57/BL6 mice that developed mechanical hypersensitivity after ischaemic injury to the sciatic nerve. Briefly, the animals were anaesthetized and injected i.v. with the photosensitizing dye erythrosine B. Vertebral segments T12 to T13 in rats or the sciatic nerve in mice were exposed and irradiated under an argon ion laser for 10 min or 45 s, respectively. In rats, mechanical hypersensitivity to pressure with von Frey hairs, the response to brushing and decreasing cold temperature were tested in the flanks or upper back areas. In mice, mechanical hypersensitivity on the hind paw to von Frey hairs and response to cold following a drop of acetone were measured. Sinomenine was administered i.p. in rats and p.o. in mice at 10:00 and 16:00, twice a day for 5 days. Response threshold before and 2 h after drug administration at 10.00 h was recorded.
Repeated administration of sinomenine at 10 or 20 mg/kg twice a day, doses that have no analgesic effect as single injection, alleviated mechanical, but not cold allodynia in spinally injured rats and the effect was maintained during the 5 day treatment period with no signs of tolerance. Furthermore, the pre-drug response threshold was significantly elevated during repeated treatment with 20 mg/kg sinomenine. Sinomenine administered at 40 mg/kg twice a day for 5 days significantly reduced mechanical and cold alldoynia, elevated pre-drug response threshold without tolerance development in spinally injured rats. Similarly, sinomenine at 80 mg/kg twice a day for 5 days significantly reduced mechanical allodynia in mice with sciatic nerve injury and increased pre-drug response threshold with no sign of tolerance. The effect of sinomenine on response threshold persisted for days after termination of the 5 day drug administration.
The results suggest that repeated administration of simomenine produced an enhanced anti-allodynic effect without tolerance in rodent models of neuropathic pain.
Sinomenine may be tested as a novel analgesic in treating some forms of chronic neuropathic pain in patients.
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ABSTRACT: Low back pain is a challenge for clinicians and researchers, due to the large variability in clinical presentation, lack of consensus regarding diagnostic criteria or clinical classification; wide variation in course and prognosis, and limited success in identifying effective treatments. However, increasing research efforts has generated an expanding body of evidence on the epidemiology, prognosis and treatment of back pain. This paper presents four key developments in research and clinical practice, and describes how these can influence the future direction of back pain research: (1) the increasing awareness of the impact of low back pain on population health; (2) new approaches to describing and investigating course and prognosis of back pain; (3) the need to better understand the bio-psycho-social mechanisms or pathways that explain impact and long-term outcomes in order to inform intervention research; and (4) the potential for stratified models of care to improve patient outcomes and efficiency of care for back pain.
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ABSTRACT: Over recent years there has been a growing need for patients to be sent home from hospital with prescribed opioids for ongoing management of their acute pain. Increasingly complex surgery is being performed on a day-stay or 23-hour-stay basis and inpatients after major surgery and trauma are now discharged at a much earlier stage than in the past. However, prescription of opioids to be self-administered at home is not without risk. In addition to the potential for acute adverse effects, including opioid-induced ventilatory impairment and impairment of driving skills, a review of the literature shows that opioid use continues in some patients for some years after surgery. There are also indications that over-prescription of discharge opioids occur with a significant amount not consumed, resulting in a potentially large pool of unused opioid available for later use by either the patient or others in the community. Concerns about the potential for harm arising from prescription of opioids for ongoing acute pain management after discharge are relatively recent. However, at a time when serious problems resulting from the non-medical use of opioids have reached epidemic proportions in the community, all doctors must be aware of the potential risks and be able to identify and appropriately manage patients where there might be a risk of prolonged opioid use or misuse. Anaesthetists are ideally placed to exercise stewardship over the use of opioids, so that these drugs can maintain their rightful place in the post-discharge analgesic pharmacopoeia.
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