These findings suggest that administration of a mixture of the three PIs increases Dyn A (1-17)- or (1-13)-induced antinociception under physiological conditions without toxicity.

Neuropathic pain (NeP) results from injury to, or disease of, the peripheral or central components of the neural systems involved in pain. In contrast to inflammatory pain, NeP can persist after healing from the initial injury has resolved. Antipyretic agents, such as non-steroidal anti-inflammatory drugs, steroids, and acetaminophen are ineffective, while specific agents such as gabapentinoids, antidepressants, antiepileptics, and opioids are effective in treating NeP. In this review, we address the definition of NeP, pharmacotherapy for NeP in Japan, pain classification, setting goals for successful NeP medication, and the Japanese algorithm for the pharmacotherapy of NeP with specific prescription guidance. (J Nippon Med Sch 2017; 84: 258 267)

Our group has earlier demonstrated that three enzymes sensitive to peptidase inhibitors (PIs), amastatin (A)-, captopril (C)-, and phosphoramidon (P), played an important role in inactivation of enkephalins at the spinal level. Dynorphin-converting enzyme (DCE) hydrolyzes dynorphin (Dyn) A (1-17) or Dyn A (1-13) mainly at the Arg 6 -Arg 7 bond. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N-and C-terminals, respectively. The purpose of the present study was to evaluate the antinociceptive potency and toxicity of intrathecal administered Dyn A (1-17), Dyn A (1-13), or Dyn A (1-6) under pretreatment with ACP and/or the DCE inhibitor p-hydroxymercuribenzoate (PHMB). The effect of these PIs on Dyn A (1-17)-induced inhibition of electrically-evoked contractions in mouse vas deferens was also investigated. The inhibitory potency of Dyn A (1-17) on electrically-evoked contractions in mouse vas deferens under pretreatment with ACP was higher than that with AC, AP, or CP. Pretreatment with ACP augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50-or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with ACP and PHMB induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or DynA (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat.

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