A memoir of my research on pain and analgesia for 39 years

Abstract

This review describes my research for the past 39 years regarding the pharmacology of pain and analgesia. We have demonstrated that the descending noradrenergic system is involved in the analgesic effect of morphine injected into the nucleus reticularis gigantocellularis, and that noradrenaline exerts antinociception mediated by α-adrenoceptors. We have found that noxious mechanical and thermal stimuli to the skin increase the release of substance P and somatostatin, respectively, from the dorsal horn in situ, and that noradrenaline inhibits the release of substance P and glutamate from primary afferents. We developed an animal model of cancer pain using melanoma cells. We have shown that the suppression of cancer pain results in the inhibition of tumor growth and lung metastasis, and that melanoma cells release several algogenic substances including ATP, endothelin-1, and bradykinin. We investigated neuropathic allodynia induced by the chemotherapeutic drugs paciltaxel, oxaliplatin, vincristine, and bortezomib. Single administration of these drugs caused allodynia with similar time-courses. However, antiallodynic actions of adjuvant analgesics, including gabapentin and limaprost, were dependent on the chemotherapeutic drugs used. Limaprost experiments have revealed that a decrease in peripheral blood flow is involved in allodynia exacerbation after the administration of paciltaxel and oxaliplatin. We have developed animal models of herpetic pain and postherpetic neuralgia using herpes simplex virus 1. We have demonstrated that nitric oxide, prostaglandin E2, and galectin-3 are involved in herpetic allodynia, that risk factors associated with postherpetic allodynia include severe herpetic pain, nociceptin, and major histocompatibility complex, and that deafferentation and nitric oxide are involved in postherpetic allodynia.