The cause for the increased sensitivity of fibromyalgia (FM) patients to painful stimuli is unclear but sensitization of dorsal horn spinal cord neurons has been suggested. There, critical changes of sensory information occur which depend on the plasticity of second-order neurons and descending pain modulation, including facilitation and inhibition. This study used repetitive stimuli that produce temporal-summation-of-second-pain (TSSP) and central sensitization, relevant mechanisms for patients with chronic pain. We examined spinal cord neural activation during TSSP in FM patients and healthy controls (HC) and used its functional connectivity with several brainstem nuclei to model the observed blood-oxygen-level-dependent (BOLD) time-course with pain ratings. Methods: 16 HC and 14 FM participants received repetitive heat stimuli to the hand at .4 Hz to achieve TSSP during functional imaging with a 3T-Philips Achieva MRI scanner. Stimuli were adjusted to each individual's pain sensitivity to achieve maximal pain ratings of 50 ± 10 on a numerical pain scale (0-100). Using a 16-channel neuro-vascular coil multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. Results: During repetitive, sensitivity-adjusted heat stimuli, pain ratings of all subjects increased as predicted, consistent with TSSP. HC and FM participants had similar temporal patterns of spinal activation: initial BOLD increase followed by de-activation. Structural equation modeling showed that the observed spinal activity during TSSP was associated with more BOLD activity across/within the brainstem in FM subjects than HC, suggesting differences in pain modulation.

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Quantitative sensory testing (QST) is used to systematically interrogate normal responding and alterations of nervous system function, including pain-related central sensitization (CS). However, up to now, QST of CS in human subjects has been mostly focused on temporal summation of second pain (TSSP), has been difficult to perform, and has been associated with low reliability. In contrast, slow ramp & hold (RH) procedures are simpler tests of temporal summation and easier to perform. We examined the usefulness of RH procedures as reliable generators of CS using 2 validated QST procedures: decay of pain aftersensations and wind-down. Twenty-seven pain-free subjects (74% female) were enrolled into the study. Trains of sensitivity-adjusted TSSP or RH heat stimuli were applied to the hands of participants to achieve moderate temporal pain summation (50 Numerical Rating Scale [NRS] [0−100]). Fifteen-second aftersensations and 30-second wind-down related to TSSP or RH were used for CS comparisons. Reliability of all test procedures was tested over 24 hours. Use of sensitivity-adjusted TSSP and RH heat stimuli resulted in average pain ratings of 48.2 and 49.6 NRS, respectively. Aftersensations or wind-down decay were not significantly different after either TSSP or RH, (all P > .05), indicating that each procedure achieved similar levels of short-term CS. Sensitivity-adjusted RH stimuli were well tolerated and resulted in reliable pain increases of »50 NRS. The magnitude of short-term CS, determined by aftersensations and wind-down was similar after sensitivity-adjusted TSSP and RH stimuli (P > .05), suggesting that pain facilitation of healthy participants and likely chronic pain patients can not only be tested with TSSP but also with RH procedures. Perspective: This article examines the ability of RH procedures to generate similar central sensitivity augmentation than TSSP. The results suggest that RH is similarly well suited as TSSP to explore central pain mechanisms in healthy subjects and most likely also in chronic pain patients.

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Background Pain is a dynamic phenomenon dependent on the balance of endogenous excitatory and inhibitory systems, which can be characterized by quantitative sensory testing. Many previous studies of pain modulatory capacity of patients with fibromyalgia syndrome (FM) have reported decreased pain inhibition or increased pain facilitation. This is the first study to assess pain modulation, including conditioned pain modulation (CPM) and temporal pain summation, in the same healthy control (HC) and FM participants. Methods Only sensitivity-adjusted stimuli were utilized for testing of conditioned pain modulation (CPM) and temporal pain summation in 23 FM patients and 28 HC. All subjects received sensitivity-adjusted ramp-hold (sRH) during testing of pain facilitation (temporal summation) and pain inhibition (CPM). CPM efficacy was evaluated with test stimuli applied either concurrently or after application of the conditioning stimulus. Finally, the effects of CPM on pressure pain thresholds were tested. Results FM subjects required significantly less intense test and conditioning stimuli than HC participants to achieve standardized pain ratings of 50 ± 10 numerical rating scale (NRS) ( p = 0.03). Using such stimuli, FM subjects’ temporal pain summation and CPM efficacy was not significantly different from HC (all p > 0.05), suggesting similar pain facilitation and inhibition. Furthermore, the CPM efficacy of FM and HC participants was similar regardless of whether the test stimuli were applied during or after the conditioning stimulus ( p > 0.05). Conclusion Similar to previous studies, FM participants demonstrated hyperalgesia to heat, cold, and mechanical stimuli. However, using only sensitivity-adjusted stimuli during CPM and temporal summation testing, FM patients demonstrated similarly effective pain inhibition and facilitation than HC, suggesting that their pain modulation is not abnormal.