Peripheral effects of opioids and nociceptin in neuropathic pain

Recent studies have pointed to the role of peripheral receptors in chronic pain process. They are located on nerve fibers, which project to dorsal root ganglion (DRG). We demonstrated using RT PCR method that peripheral nerve injury caused a reduction in a number of mu‐opioid receptors in DRG. We also checked the peripheral effects of opioid (morphine, DAMGO, EM‐1, EM‐2) and ORL‐1 (nociceptin) receptor agonists. Our findings show that intraplantarly administered agonists were effective in antagonizing allodynia. Peripheral mu‐opioid and ORL1 receptors mediate the observed effects as was evidenced by treatment with naloxone methiodide, which is only peripherally active. The present results demonstrated that opioids after peripheral treatment, in spite of decreased expression of mu‐opioid receptor mRNA in DRG, are effective and their peripheral use may eliminate central unwanted side‐effects.Acknowledgement:   Supported by EU grant (No. QLRT‐2001‐02919).