Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin–saporin

• Published in: Neurotoxicology (Park Forest South) 2009-11, Vol.30 (6), p.1096-1106
• Main Authors: Cao, Fei, Chen, Sha-Sha, Yan, Xiao-Feng, Xiao, Xing-Peng, Liu, Xi-Jiang, Yang, Shao-Bing, Xu, Ai-Jun, Gao, Feng, Yang, Hui, Chen, Zhi-Jun, Tian, Yu-Ke
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - toxicity; Animals; Biological and medical sciences; CD11b Antigen - metabolism; Dermorphin; Descending facilitation; Drinking - drug effects; Eating - drug effects; Echocardiography - methods; Enzyme-Linked Immunosorbent Assay - methods; Gene Expression Regulation - drug effects; Glial Fibrillary Acidic Protein - metabolism; Hyperalgesia - mortality; Immunotoxins - toxicity; Interleukin-1beta - metabolism; Male; Medical sciences; Medulla Oblongata - cytology; Microinjections; Motor Activity - drug effects; Neurons - drug effects; Neurons - metabolism; Opioid Peptides - toxicity; Opioid receptor; Pain Measurement - methods; Pain Threshold - drug effects; Rats; Rats, Wistar; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Ribosome Inactivating Proteins, Type 1 - toxicity; Rostral ventromedial medulla; Saporin; Toxicology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2009.06.004

Descending facilitation from the rostral ventromedial medulla (RVM) contributes to some pathological pain states. The intra-RVM microinjection with dermorphin–saporin could specifically abolish this facilitation in rodent models by selectively ablating the RVM neurons expressing mu opioid receptors. Thus, this targeted lesion may be an alternative mechanism-based approach for intractable pain. This research was performed to investigate potential side effects after a single intra-RVM application of dermorphin–saporin in rats. Results showed though some acute cardiovascular signs were observed with dermorphin–saporin, the treatment exhibited no long-lasting significant influence on some physiological functions for up to 3-month observation period, including normal sensory function, locomotor activity, ingestive behaviors, body weight, rectal temperature, respiratory rate, heart rate, systolic blood pressure, cardiac structure and function. Moreover, there were only mild microglial responses on day 7 post-microinjection, while no significant increase in the immunostaining of astrocytes and no noticeable up-regulation in the production of proinflammatory cytokines were detected in the RVM treated with dermorphin–saporin. Taken together, these data would suggest that this selective ablation of mu opioid receptor bearing descending facilitatory neurons in the RVM with dermorphin–saporin did not elicit the long-standing evident adverse toxicity in terms of some physiological parameters and neurochemical alterations we determined, plausibly providing us a safe and reliable approach to treat some intractable pain.