Neural - Glial Interaction in Neuropathic Pain

Lesioning of the nervous system can produce a form of pathological pain called “neuropathic pain” that is characterized by sensory deficit, burning sensation, hyperalgesia and allodynia (Cui et al., 2000). The mechanisms underlying neuropathic pain have been studied extensively. Abundant evidence has indicated that aside from the neural component, the non-neural cells of the CNS, such as glial cells, have important roles in the pathogenesis of pain (Coyle, 1998). To a certain extent, glial activation is triggered secondary to injury. Glial cells play an important role in the initiation, development and maintenance of persistent neuropathic pain. Both microglia and astrocytes are activated in the spinal cord after nerve injury, and pain is amplified when glia become activated (Mika, 2008). It has been hypothesized that neuropathic pain and morphine tolerance share some common pathological mechanisms (Mayer et al., 1999). Many studies have indicated that neuropathic pain leads to reduced morphine efficacy and the rapid development of morphine tolerance. The glia become activated in response to the repeated administration of morphine, which leads to the release of proinflammatory mediators and may oppose opioid analgesia by altering neuronal excitability (Campbell et al., 2006). It is not clear how opioids activate microglia in the spinal cord, but previous work by Hutchinson’s team suggested the possible involvement of toll-like receptor 4 (TLR4) (Tanga et al., 2005). In this study, we tried to understand the role of microglia in morphine tolerance and also examine some possible methods for improving the efficacy of morphine to control neuropathic pain.