Background: Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the... Show moreBackground: Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm. Methods: Twenty-two healthy subjects participated in the study. We performed a task-based fMRI study using a randomized crossover design. Subjects were scanned under two conditions (spinal anesthesia or control) at two-time points: before and after spinal anesthesia. Spinal anesthesia resulted in sensory loss up to dermatome Th6. Calibrated heat-pain stimuli were administered to the right forearm (C8-Th1) using a box-car design (blocks of 10s on/25s off) during MRI scanning. Pain perception was measured using a visual analogue scale (1–100) at the beginning and the end of each session. Generalized estimating equations were used to examine the effect of intervention by time by order on pain scores. Similarly, higher level effects were tested with appropriate general linear models (accounting for within-subject variations in session and time) to examine: (1) Differences in BOLD response to pain stimulus under spinal anesthesia versus control; and (2) Effects of spinal anesthesia on pain-related modulation of the cerebral activation. Results: Complete fMRI data was available for eighteen participants. Spinal anesthesia was associated with moderate pain score increase. Significant differences in brain response to noxious thermal stimuli were present in comparison of spinal versus control condition (post—pre). Spinal condition was associated with higher BOLD signal in the bilateral inferior parietal lobule and lower BOLD signal in bilateral postcentral and precentral gyrus. Within the angular regions, we observed a positive correlation between pain scores and BOLD signal. These observations were independent from order effect (whether the spinal anesthesia was administered in the first or the second visit). However, we did observe order effect on brain regions including medial prefrontal regions, possibly related to anticipation of the experience of spinal anesthesia. Conclusions: The loss of sensory and motor activity caused by spinal anesthesia has a significant impact on brain regions involved in the sensorimotor and cognitive processing of noxious heat pain stimuli. Our results indicate that the anticipation or experience of a strong somatosensory response to the spinal intervention might confound and contribute to increased sensitivity to cognitive pain processing. Future studies must account for individual differences in subjective experience of pain sensation within the experimental context Show less
BACKGROUND It is generally accepted that a neuraxial blockade strengthens the sedative effects of propofol. Deafferentation caused by neuraxial blockade is thought to play a key role. OBJECTIVES... Show moreBACKGROUND It is generally accepted that a neuraxial blockade strengthens the sedative effects of propofol. Deafferentation caused by neuraxial blockade is thought to play a key role. OBJECTIVES The objective is to determine whether epidural blockade affects the bispectral index (BIS) of propofol and two other pharmacodynamic endpoints, mean arterial pressure (MAP) and cardiac output (CO). DESIGN Randomised, placebo-controlled study. SETTING University hospital. PATIENTS Patients scheduled for surgery needing epidural analgesia. INTERVENTION 28 ASA one or two patients received 0, 50, 100 or 150 mg of epidural ropivacaine. After stabilisation of the epidural blockade, propofol was given by target-controlled infusion. The propofol plasma target concentrations were increased at 6-min intervals from 0 to 1, 2.5, 4 and 6 mu g ml(-1). The study was performed before surgery. MAIN OUTCOME MEASURES Three endpoints, BIS, mean arterial blood pressure and CO were measured from baseline (prior to the administration of epidural ropivacaine) until 2 h after the start of propofol infusion. The propofol concentration-effect data were analysed to determine the interaction between epidural blockade and propofol sedation. RESULTS In the absence of propofol, the increase in number of epidural blocked segments from 0 to 15.5 (range 6 to 21) reduced the MAP by 30%, without affecting BIS or CO. In the absence of epidural blockade, the increase in propofol concentration to 6 mu g ml(-1) reduced BIS, MAP and CO. When combined, epidural anaesthesia and intravenous propofol exhibited no pharmacodynamic interaction on any of the three endpoints. In addition, epidural blockade did not affect the propofol effect-site equilibration half-life for its haemodynamic effects (11.5 +/- 0.5 min) or for its effects on the BIS (4.6 +/- 0.4 min). CONCLUSION Epidural blockade reduces the propofol requirements for sedative end points. This is not the result of a pharmacodynamic interaction. Show less
Sitsen, E.; Velzen, M. van; Rover, M. de; Dahan, A.; Niesters, M. 2020
Introduction: Spinal anesthesia induces short-term deafferentation and causes connectivity changes in brain areas involved in endogenous pain modulation. We determined whether spinal anesthesia... Show moreIntroduction: Spinal anesthesia induces short-term deafferentation and causes connectivity changes in brain areas involved in endogenous pain modulation. We determined whether spinal anesthesia alters pain sensitivity and offset analgesia. Offset analgesia is a manifestation of endogenous pain modulation and characterized by profound analgesia upon a small decrease in noxious stimulation.Methods: In this randomized controlled crossover trial, static thermal pain responses and offset analgesia were obtained in 22 healthy male volunteers during spinal anesthesia and control conditions (absence of spinal anesthesia). Pain responses and offset analgesia were measured on a remote skin area above the upper level of anesthesia (C8/Th1).Results: Following spinal injection of the local anesthetic, the average maximum anesthesia level was Th6. Static pain scores at C8/Th1 were higher during spinal anesthesia compared to control: 59.1 +/- 15.0 mm (spinal anesthesia) versus 51.7 +/- 19.7 mm (control; p = 0.03). Offset analgesia responses were decreased during spinal analgesia: pain score decrease 79 +/- 27% (spinal anesthesia) versus 90 +/- 17% (control; p = 0.016).Discussion: We confirmed that spinal anesthesia-induced deafferentation causes hyperalgesic responses to noxious thermal stimulation and reduced offset analgesia at dermatomes remote and above the level of deafferentation. While these data suggest that the reduction of offset analgesia has a central origin, related to alterations in brain areas involved in inhibitory pain control, we cannot exclude alternative (peripheral) mechanisms. Show less
