Cutaneous C-fiber pain abnormalities of fibromyalgia patients are specifically related to temporal summation

Abstract 

Temporal summation of “second pain” (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed ‘windup’. TSSP is dependent on stimulus frequency (⩾0.33Hz) and is relevant for central sensitization and chronic pain. We have previously shown that compared to normal controls (NC), fibromyalgia (FM) subjects show abnormal TSSP, requiring lower stimulus intensities/frequencies to achieve similar TSSP. However, it is unknown whether abnormal TSSP in FM is influenced by peripheral sensitization of C-fiber nociceptors and/or bias in pain ratings. Thus, we evaluated 14 FM subjects and 19 NC with pain threshold tests to selective C-fiber stimulation, 30s heat stimuli, and repetitive brief (1.5s) heat pulses at 0.33Hz using a contact heat stimulator (CHEPS). The intensity of heat pulses was varied to achieve maximal TSSP ratings of 45±10 (numerical pain scale 0–100) in both FM and NC groups. We found that NC and FM subjects had similar pain thresholds to C-fiber stimulation and yet FM subjects required lower heat pulse temperatures to generate the same magnitudes of TSSP (p<.05). This combination of findings does not support peripheral sensitization and suggests central TSSP abnormalities in FM subjects. In a second experiment, all aspects of individually adjusted TSSP heat pulses were kept the same except that the baseline temperature (BT) between heat pulses was surreptitiously alternated between 35°C and 40°C. These changes of BT resulted in significantly greater TSSP ratings of FM subjects compared to NC subjects, both at 35°C and at 40°C, but did not change their response to the first heat pulse of a stimulus train. These findings provide strong support for alterations of central pain sensitivity and not peripheral sensitization or rating bias as responsible for TSSP differences between NC and FM subjects.

Keywords: Temporal summation, Hyperalgesia, Fibromyalgia, Dermatome, Chronic pain, Central sensitization, Psychophysical testing, Rating bias, C-fiber