Distribution of Spinal Sensitization Evoked by Inflammatory Pain Using Local Spinal Cord Glucose Utilization Combined with 3H-Phorbol 12,13-Dibutyrate Binding in Rats

Aims. Hyperalgesia following tissue injury is induced by plasticity in neurotransmission. Few investigators have considered the ascending input which activates the superficial of spinal cord. The aim was to examine neurotransmission and nociceptive processing in the spinal cord after mustard-oil (MO) injection. Both in vitro and in vivo autoradiographs were employed for neuronal activity and transmission in discrete spinal cord regions using the 14C-2-deoxyglucose method and 3H-phorbol 12,13-dibutyrate (3H-PDBu) binding sites. Methods. To quantify the hyperalgesia evoked by MO, the flinching was counted for 60？min after MO (20%, 50？μL) injection in Wistar rats. Simultaneous determination of 14C-2-deoxyglucose and 3H-PDBu binding was used for a direct observation of neuronal/metabolic changes and intracellular signaling in the spinal cord. Results. MO injection evoked an increase in flinching for 60？min. LSCGU significantly increased in the Rexed I-II with 3H-PDBu binding in the ipsilateral side of spinal cord. Discussion. We clearly demonstrated that the hyperalgesia is primarily relevant to increased neuronal activation with PKC activation in the Rexed I-II of the spinal cord. In addition, functional changes such as “neuronal plasticity” may result in increased neuronal excitability and a central sensitization. 1. Introduction A number of reports have characterized the mechanisms underlying pathological pain, primarily by investigating pain-producing substances in peripheral sensory receptors and pain transmitters in the spinal cord, as well as the associated pain pathways. More recent attempts have gradually increased understanding through the investigation of neuroglial interactions and spinal sensory nerves and the modulation of spinal pain transmission in relation to refractory hyperalgesia. It has been suggested that following tissue damage/inflammation, repetitive pain receives contributions from neuronal plasticity in the processes of nociception. Repetitive noxious stimulation to primary afferent C fibers produces a sustained hyperalgesia [1] leading to exaggerated pain-related behavior, for example, shaking or flinching (“hyperalgesia”). Woolf and Salter [2] proposed that neuroplastic changes in spinal synaptic transmission are the primary mechanism behind persistent spontaneous pain and hyperalgesia following such peripheral tissue and nerve injury. Ample research conducted subsequently suggests that mitogen associated protein kinase family; MAPKs (extracellular signal-regulated kinase 1/2: ERK1/2, p38-MAPK, and c-jun N-terminal kinase: JNK)