Inflammation-induced hyperalgesia: effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.

BACKGROUND: Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect. METHODS: In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8 ng/kg Escherichiacoli), low-dose LPS (0.4 ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6h after injection of LPS or placebo. RESULTS: LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3h after injection of the moderate dose of LPS (0.8 ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood. CONCLUSIONS: Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8 ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions.

Short-term effects of two deep dry needling techniques on pressure pain thresholds and electromyographic amplitude of the lumbosacral multifidus in patients with low back pain - a randomized clinical trial.

Objectives: The purpose of this study was to compare the effects of deep dry needling (DN) with and without needle manipulation on pressure pain thresholds (PPTs) and electromyographic (EMG) amplitude of the lumbosacral multifidus (LM) in adults with low back pain (LBP). Methods: Participants were randomized into two treatment groups: with needle manipulation (n = 21) and without needle manipulation (n = 21). All participants received a single session of the assigned DN intervention. PPTs and EMG amplitude of the LM muscle were collected three times: before DN, immediately after DN, and one week after DN. Results: The needle manipulation group had a significantly greater increase in PPT immediately after the intervention and at the one-week follow-up as compared to the no needle manipulation group. The increase of PPT in the needle manipulation group was significant immediately after the intervention, and the increase remained significant at the one-week follow-up. However, there was no significant difference in EMG amplitude of the LM muscle between groups across the three time points. Discussion: Deep DN with needle manipulation appeared to reduce mechanical pressure sensitivity more than DN without manipulation for patients with LBP. Although a single session of DN could reduce pressure pain sensitivity, it may not be sufficient to improve LM muscle function. Level of Evidence: 1b. Trial registration numbers: NCT03970486.

Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II.

Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3α5α-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5α-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3α5α-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds.

Hand-arm vibration syndrome: clinical characteristics, conventional electrophysiology and quantitative sensory testing.

OBJECTIVE: Workers exposed to vibrating tools may develop hand-arm vibration syndrome (HAVS). We assessed the somatosensory phenotype using quantitative sensory testing (QST) in comparison to electrophysiology to characterize (1) the most sensitive QST parameter for detecting sensory loss, (2) the correlation of QST and electrophysiology, and (3) the frequency of a carpal tunnel syndrome (CTS) in HAVS. METHODS: QST, cold provocation tests, fine motor skills, and median nerve neurography were used. QST included thermal and mechanical detection and pain thresholds. RESULTS: Thirty-two patients were examined (54 ± 11 years, 91% men) at the more affected hand compared to 16 matched controls. Vibration detection threshold was the most sensitive parameter to detect sensory loss that was more pronounced in the sensitivity range of Pacinian (150 Hz, x12) than Meissner's corpuscles (20 Hz, x3). QST (84% abnormal) was more sensitive to detect neural dysfunction than conventional electrophysiology (37% abnormal). Motor (34%) and sensory neurography (25%) were abnormal in HAVS. CTS frequency was not increased (9.4%). CONCLUSION: Findings are consistent with a mechanically-induced, distally pronounced motor and sensory neuropathy independent of CTS. SIGNIFICANCE: HAVS involves a neuropathy predominantly affecting large fibers with a sensory damage related to resonance frequencies of vibrating tools.