Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo-controlled study

Abstract

Fibromyalgia (FM) syndrome is characterized by pain and widespread hyperalgesia to mechanical, thermal, and electrical stimuli. Despite convincing evidence for central sensitization of nociceptive pain pathways, the role of peripheral tissue impulse input in the initiation and maintenance of FM is unclear. Therefore this randomized, double-blind, placebo-controlled trial of 22 female normal controls (NCs) and 28 female FM subjects tested the effects of trapezius muscle (TrapM) tender point injections with 1% lidocaine on local pain thresholds as well as on remote heat hyperalgesia at the forearm. Prior to muscle injections shoulder pain was standardized by tonic mechanical muscle stimulation, resulting in local pain ratings of 4.0+/-0.5 VAS units. Tonic muscle stimulation was interrupted for the TrapM injections but was continued afterwards at the same level. NC as well as FM subjects experienced significant increases of TrapM pressure pain thresholds from lidocaine injections but not from placebo injections (p<0.001). Additionally, heat hyperalgesia of FM participants was significantly reduced at areas remote from the injection site (forearm) by lidocaine but not by placebo (p=0.02). Neither lidocaine nor saline injections significantly affected clinical FM pain ratings, a result most likely due to the very low dose of lidocaine (50mg) used in this trial.

Conclusion: Lidocaine injections increased local pain thresholds and decreased remote secondary heat hyperalgesia in FM patients, emphasizing the important role of peripheral impulse input in maintaining central sensitization in this chronic pain syndrome; similar to other persistent pain conditions such as irritable bowel syndrome and complex regional pain syndrome.

Figure 1

Flow diagram of study procedures. Two groups of NC and 2 groups of FM participants received either placebo or lidocaine injections into the TrapM TP. PPTs were tested at the shoulder (primary hyperalgesia) and 10 sec thermal ramps were applied to the forearms (secondary hyperalgesia) before and after the injections. The left side of this figure shows the pressure device used for tonic mechanical TrapM stimulation. Pressurized air was applied to the muscle stimulator resulting in expansion of a telescoping prong (diameter 1cm) for up to 4 cm. A calibrated force transducer mounted to the tip of the prong provided real-time information on an electronic display. This information was used to continuously adjust tonic pressure stimuli to the TrapM TP. TrapM = trapezius muscle; TP = tender point; PPT = pressure pain threshold; for detailed descriptions of sections; A–F = see text for more details (2.2).

Figure 2

Pressure pain (Panel A) and heat pain sensitivity (Panel B) of NC and FM subjects. All participants underwent prolonged sensitivity adjusted tonic pressure stimulation at the TrapM and 10 sec sensitivity adjusted heat stimulation at the forearm Average tonic pressure used to achieve shoulder pain ratings of 4.0 ± 0.5 VAS units was 2.3 kg for NC (n =16) and 1.1 kg for FM participants (n = 21) (p < .001) (Panel A). To achieve similar intensity levels of heat pain ratings at the forearm, stimulus temperatures of 48.7 °C and 47.4 °C were needed for NC (n = 22) and FM subjects (n = 28), respectively (p < .001) (Panel B). Open circles = NC-Placebo; open diamonds = NC-Lidocaine; filled circles = FM-Placebo; filled diamonds = FM-Lidocaine

Figure 3

Effects of lidocaine or placebo injections on pressure pain thresholds (PPT) at the TrapM. PPT [mean (SD)] were measured with an electronic algometer at baseline, before, and after shoulder injections with lidocaine or placebo. PPTs were significantly lower in FM subjects compared to NC (p < .001). However, only lidocaine but not normal saline placebo resulted in significant increases of PPTs in NC and FM participants (p = .001). TrapM = trapezius muscle

Figure 4

Effects of muscle injections on sensitivity adjusted pressure pain ratings at the TrapM. Tonic pressure stimuli at the TrapM were adjusted to each individual’s mechanical pain sensitivity to achieve maximal pain ratings of 4.0 ± 0.5 VAS units. Initially, average (SD) pain ratings of sensitivity adjusted tonic shoulder stimuli of NC-PL and NC-LI were 3.9 (0.4) VAS units and 4.0 (0.4) VAS units, respectively (Tonic-start). Similarly, the tonic TrapM pain ratings of FM-PL and FM-LI was 3.9 (0.5) VAS units and 4.6 (0.7) VAS units, respectively. After 30 sec of tonic stimulation (Tonic+30 sec) the shoulder pain of NC-PL and NC-LI participants significantly decreased to 2.4 (1.2) and 1.8 (0.9) VAS units (all p = .001), respectively, but did not statistically change in FM subjects [FM-PL = 4.6 (1.6) and FM-LI = 5.3 (2.0) VAS units (all p > .05)] After lidocaine or placebo injections into TrapMs tonic pressure pain ratings decreased significantly in NC and FM subjects’ [NC-PL = 1.3 (1.3); NC-LI = 0.8 (0.7); FM-PL = 3.24 (2.1); FM-LI = 3.3 (1.9)] (all p < .004). ns = non-significant; TrapM = trapezius muscle.

Figure 5

Heat pain ratings of NC and FM subjects at the forearm. For this experiment, 10 sec heat stimuli to the forearm were individually adjusted to achieve maximal pain ratings of 4.0 ± 0.5 VAS units in NC and FM participants at baseline. Average (SD) pain ratings of 10 sec heat pulses did not significantly change during all 3 experimental conditions (baseline, tonic TrapM stimulation, TrapM injection) in NC-PL, FM-PL and NC-LI subjects. Whereas forearm heat pain ratings of FM-LI participants did not change during tonic pressure pain stimulation, a significant decrease in heat hyperalgesia was observed after lidocaine injections (p = .007). Planned comparisons of medication effects between FM-LI and FM-PL showed significantly less heat hyperalgesia in the lidocaine group after the injection (p = .02). BL = baseline; Tonic = tonic shoulder stimulation; Tonic+Inj = tonic shoulder stimulation after TrapM injections with either lidocaine or placebo.