Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: an fMRI study.

The cause for the increased sensitivity of patients with fibromyalgia (FM) 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 patients with FM 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. Sixteen HC and 14 FM participants received repetitive heat stimuli to the hand at 0.4 Hz to achieve TSSP during functional imaging with a 3 T-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 neurovascular coil, multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. 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 deactivation. 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.NEW & NOTEWORTHY "Windup" and its behavioral correlate "temporal-summation-of-second pain" (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.

Usefulness of Ramp & Hold Procedures for Testing of Pain Facilitation in Human Participants: Comparisons With Temporal Summation of Second Pain.

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.