Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain

The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long-term neuropathic pain by 50% (AD₅₀) was calculated and compared to the AD₅₀ in the immediate postoperative period. We found that long-term neuropathic pain could be adequately reduced by buprenorphine. However, the AD₅₀ in neuropathic pain was significantly higher relative to the AD₅₀ in the short-term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short-term and long-term AD₅₀, characterized by a saturating effect. In fact, if the AD₅₀ soon after surgery was low, the AD₅₀ increase in the long-term neuropathic pain was threefold. By contrast, if the AD₅₀ soon after surgery was high, the AD₅₀ in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.