Peripheral and spinal mechanisms of nociceptive transmission in a rat model of fibromyalgia

Fibromyalgia (FM) is characterized by chronic widespread pain with mecha nical allodynia and hyperalgesia. However, the neural mechanisms of nociception and pain are largely unknown. The aim of this study was to examine the responsiveness of peripheral nociceptive afferents and super ficial dorsal horn (SDH) neurons by using a manifest rat model of FM, that was induced by reserpine (RES) injection. Repeated administration of RES ( 1 mg/kg, s.c., once daily for three consecutive days) caused a significant decrease in the mechanical withdrawal threshold of the plantar skin. Single– fiber electrophysiological recordings in vitro revealed that mechanical responses of mechano–responsive C–fibers were increased, although the proportion of mechano–responsive C–nociceptors was paradoxically de -creased. Next, we performed in vivo extracellular recordings of the SDH neurons. Although the SDH neurons showed mechanical stimulus intensity– dependent increases in the discharge rate both in the vehicle (VEH) and the RES–injected group, the response magnitude was significantly greater in the RES–injected group. Some SDH neurons in the RES–injected rats exhibited spontaneous firing with low frequencies, although those in the VEH– injected rats did not. These results suggest that increased mechanical sensitivity of the mechano–responsive C–fibers and the SDH neurons are involved in mechanical allodynia and hyperalgesia in a rat model of RES– induced pain. Similar mechanisms may underlie in patients with FM.