The combination of morphine and minocycline may be a good treatment for intractable post-herpetic neuralgia

Abstract

Post-herpetic neuralgia (PHN) is a devastating complication of shingles. The treatment of PHN with traditional pharmaceutical agents has various side effects. Therefore, the treatment of intractable PHN is often very time consuming, mainly because the available treatments often lead to intolerable side effects before the efficient dose can be reached. Opioids such as morphine and oxycodone are the most widely used drugs for the alleviation for severe chronic pain. A number of high quality studies demonstrated that opioids are effective in relieving neuropathic pain including PHN. Yet concerns of misuse, abuse and tolerance of opioids have, however, severely influenced their contribution to neuropathic pain, especially the tolerance that resulted in a loss of drug effect or the necessity for escalating doses to produce pain relief. The glia cells, particularly microglia and astrocytes are thought to play an important role in central sensitization. It is known that activated microglia cells produce NO, cytokines, and cyclooxygenase. All of these chemicals regulate synaptic transmissions in the central nervous system. Additionally, glia modulations showed antiallodynic and antihyperalgesic properties in various experimental pain models. Minocycline, a semisynthetic, second-generation tetracycline can potently inhibit microglial activation and proliferation. Also, the growing body of recent evidence indicates that minocycline attenuates morphine tolerance in neuropathic mice with a mechanism related to microglia. The combination of morphine and minocycline has synergetic effect. This can prevent the development of intractable PHN and attenuate morphine antinociceptive tolerance and further improve the efficacy of morphine and therefore reducing its dosage and side effects. We thereby hypothesize that the combination of morphine and minocycline may produce a duel effect of morphine antinociceptive and minocycline selectively inhibiting the activation of microglia.