Background and aims. Activated microglia play a crucial role in central sensitization leading to chronic pain. An important spinal modulator between microglial cells and dorsal horn neurons is the chemokine fractalkine (FKN). The aim was to study the spinal sensitization effects of FKN in an animal model of myofascial low back pain (LBP).

Methods. In deeply anesthetized rats, in vivo recordings of single dorsal horn neurons with input from the low back were made. Two injections of nerve growth factor (NGF; 5 days apart) into the multifidus muscle which induced neuronal hyperexcitability of dorsal horn neurons to peripheral input served as a model of myofascial LBP. The hyperexcitability was expressed in an increased proportion of neurons with convergent input from different types of tissue. The additional afferent input came exclusively from deep tissues.

Two experimental series were carried out:
1. The FKN signaling pathway was blocked by intrathecally applied neutralizing antibodies to prevent the NGF-induced hyperexcitability. 
2. FKN itself was administered intrathecally to determine whether it caused the identical hyperexcitability as two NGF injections.  

Results. The neutralizing antibodies completely prevented the NGF-induced increased proportion of neurons with convergent input (p<0,01) and input from deep tissues (p<0,05), while FKN induced the identical neuronal hyperexcitability as two NGF injections (p<0,01). 

Conclusions. The data show that FKN plays a crucial role in sensitization of dorsal horn neurons as one first step in the chronification of myofascial LBP. 

The project was supported by the Deutsche Forschungsgemeinschaft (DFG -TR 236/24, SFB1158_S01).

FRACTALKINE-INDUCED HYPEREXCITABILITY OF SPINAL DORSAL HORN NEURONS IN AN ANIMAL MODEL OF MYOFASCIAL LOW BACK PAIN