Pain Hypersensitivity and Morphine Tolerance: Shared Mechanisms?

Repeated administration of morphine renders animals tolerant to the drug and hypersensitive to pain. These two effects are strikingly similar to those induced by nerve injury. Researchers have hypothesized about a shared mechanism and have investigated neurotransmitters and signal-transduction pathways in neurons. Joyce DeLeo of Dartmouth Medical School wondered about immune cell involvement.

After studying the role of microglia in neuropathic pain for many years, DeLeo applied similar experimental strategies to study the hyperalgesia observed in morphine-dependent animals and its interactions with nerve injury.¹ First, she showed the decreased effect that morphine has on pain behaviors in her nerve injury model; this imitates the clinical problem with opiate resistance in neuropathic pain patients. Second, she found that chronic morphine treatment activated spinal microglia and concomitantly increased proinflammatory cytokines. These changes were amplified in animals with nerve injury. Given the likelihood that activated microglia enhance pain sensation, it follows that...