Electrophysiological Evaluation of Pathophysiological and Pharmacological Characteristics of Chronic Pain

Abstract

Recent studies have revealed considerable evidence for our understanding of the mechanisms underlying the development and maintenance of chronic pain including neuropathic and inflammatory pain. It is considered that plastic changes in the spinal dorsal horn contribute to the amplification of pain signaling. Moreover, persistent pain affects brain function and also the endogenous descending pain regulatory system. To characterize these pathophysiological changes and pharmacological properties in chronic pain conditions at the synaptic level, we have employed in vitro electrophysiology in slices of the spinal cord and supraspinal regions such as brainstem and hippocampus of adult mice and in vivo electrophysiology in anesthetized rats. In particular, we have successfully prepared spinal slices with an attached dorsal root, where A-fiber- or C-fiber-evoked monosynaptic excitatory postsynaptic currents or miniature excitatory postsynaptic currents were recorded from voltage-clamped dorsal horn neurons. In anesthetized rats, C-fiber-evoked field potentials were recorded from the spinal dorsal horn in response to electrical stimulation of the sciatic nerve fibers, and their long-term potentiation was elicited to mimic increased synaptic efficacy after peripheral nerve injury. Of interest is the finding that some drugs exerted the injury-specific effects on synaptic transmission, thus strongly suggesting the importance of pharmacological analysis at the synaptic level combined with electrophysiological techniques to obtain pathophysiological information and new insights into drug research in this field.