Tonic Descending Facilitation from the Rostral Ventromedial Medulla Mediates Opioid-Induced Abnormal Pain and Antinociceptive Tolerance

• DOI: 10.1523/jneurosci.21-01-00279.2001
• Publication Date: 2018-04-05T22:33:47Z
• Authors: Todd W. Vanderah; Nova M. H. Suenaga; Michael H. Ossipov; T. Philip Malan; Josephine Lai; Frank Porreca
• Keywords: Rostral ventromedial medulla

Many clinical case reports have suggested that sustained opioid exposure can elicit unexpected, paradoxical pain. Here, we explore the possibility (1) opioid-induced pain results from tonic activation of descending facilitation arising in rostral ventromedial medulla (RVM) and (2) presence such manifests behaviorally as antinociceptive tolerance. Rats implanted subcutaneously with pellets or osmotic minipumps delivering morphine displayed time-related tactile allodynia thermal hyperalgesia (i.e., “pain”); placebo saline did not change thresholds. Opioid-induced was observed while delivery continued rats were withdrawal. RVM lidocaine, bilateral lesions dorsolateral funiculus (DLF), response thresholds placebo-pelleted but blocked The intrathecal dose–response curve (DRC) morphine-pelleted displaced to right rats, indicating “tolerance.” lidocaine DLF lesion alter DRC rightward displacement seen animals. subcutaneous rats; this shift by lidocaine. data show opioids through bulbospinal RVM, increased decreases spinal potency, (3) blockade restores revealing no signal transduction. These studies offer a mechanism for allow development approaches which loss analgesic activity might be inhibited.