Translational investigation and treatment of neuropathic pain

Abstract

Neuropathic pain develops from a lesion or disease affecting the somatosensory system. Translational investigations of neuropathic pain by using different animal models reveal that peripheral sensitization, spinal and cortical plasticity may play critical roles in neuropathic pain. Furthermore, descending facilitatory or excitatory modulation may also act to enhance chronic pain. Current clinical therapy for neuropathic pain includes the use of pharmacological and nonpharmacological (psychological, physical, and surgical treatment) methods. However, there is substantial need to better medicine for treating neuropathic pain. Future translational researchers and clinicians will greatly facilitate the development of novel drugs for treating chronic pain including neuropathic pain.

Figure 1

Neuropathic pain is manifested through alterations at the peripheral, spinal, and cortical levels. At the periphery, neuropathic pain is associated with changes in the excitability of nociceptors. At the spinal cord level, long-term potentiation (LTP) of sensory excitatory synaptic transmission take place at least at similar time scales. The upregulation of postsynaptic AMPA receptors including possible recruitment of silent synapses contribute to spinal LTP. Similar to LTP reported in other central synapses, different protein kinases and possible new protein synthesis are also required. Within the cortex, neuropathic pain is associated with the induction of LTP including late-phase LTP (L-LTP) at cortical synapses. Both presynaptic and postsynaptic alterations have been observed that result in ongoing potentiated excitatory activity. Dis-inhibition of local inhibitory modulation have been also found within the spinal dorsal horn and cortical areas. Descending faciltiatory modulation from cortical and sub-cortical areas are also thought to contribute to enhanced sensory transmission in the spinal cord dorsal horn.