Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons

Abstract

Background This is a “proof of concept study” to test the hypothesis that pulsed radiofrequency, PRF, produces cell stress at the primary afferent level without signs of overt thermal damage. We assumed that cell stress would result in impairment of normal function, and used the expression of activating transcription factor 3, ATF3, as an indicator of cellular “stress”. Methods PRF (20 ms of 500-kHz RF pulses, delivered at a rate of 2 Hz; maximum temperature 42 °C) was delivered either to the sciatic nerve of adult rats in mid thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen. Controls were sham-operated or L4 axotomised. All tissues were examined 14 days after surgery. The percentage of CGRP- or ATF3-positive DRG neuronal somata was calculated using image analysis software (SigmaScan Pro 4). Results ATF3 expression was upregulated in L4 DRG neuronal cell bodies, irrespective of their size, after axotomy. It was also upregulated significantly ( p < 0.002) and selectively, in small and medium calibre L4 DRG neurons, when PRF was applied close to the DRG just distal to the intervertebral foramen. PRF did not produce any obvious cellular changes in the nerve or L4 DRG neurons when applied to the sciatic nerve in mid-thigh. Conclusion PRF has a biological effect, unlikely to be related to overt thermal damage. It appears to be selective in that it targets the group of neurons whose axons are the small diameter C and Aδ nociceptive fibres.