The Effect of Distance From Injection Site to the Brainstem Using Spinal Sufentanil

Swenson, Jeffrey D.; Owen, John; Lamoreaux, Wayne; Viscomi, Christopher M.; McJames, Scott; Cluff, Mark

doi:10.1097/00115550-200107000-00005

Cited by 28 publications

(7 citation statements)

References 16 publications

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“…Previous human (Eisenach et al 2003) and animal (Swenson et al 2001) studies reveal the potential for cephalad movement of opioids within the CSF. Individual variations in the extent of the 'upstream' spread have been reported, but it is thought that axial spinal length (distance between injection site and brainstem) is likely to play a key role (Swenson et al 2001). Furthermore, as fentanyl is slightly hypobaric relative to CSF, patient position will also contribute to the cephalad movement (Swenson et al 2001).…”

Section: Experimental Use Of Intrathecal Fentanylmentioning

confidence: 99%

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

Amann

Runnels

Morgan

et al. 2011

The Journal of Physiology

140

158

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Non-technical summary We investigated the role of thin fibre muscle afferents in the circulatory response to exercise in humans. The results not only document the importance of continuous afferent feedback from working human skeletal muscle to achieve appropriate haemodynamic and ventilatory responses to exercise but also suggest that the relative contribution of this mechanism is larger than traditionally accepted. AbstractWe investigated the role of skeletal muscle afferent feedback in circulatory control during rhythmic exercise in humans. Nine healthy males performed single leg knee-extensor exercise (15/30/45 watts, 3 min each) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. Cardiac output and femoral blood flow were determined, and femoral arterial/venous blood samples were collected during the final minute of each workload. To rule out cephalad migration of fentanyl to the brainstem, we documented unchanged resting ventilatory responses to different levels of hypercapnia. There were no haemodynamic differences between conditions at rest. However, during exercise cardiac output was ∼20% lower with fentanyl blockade compared to control (P < 0.05), secondary to a 6% and 13% reduction in heart rate and stroke volume, respectively. Throughout exercise mean arterial pressure (MAP) was reduced by 7% (P < 0.01) which is likely to have contributed to the 15% fall in femoral blood flow. However, MAP was not completely responsible for this peripheral haemodynamic change as vascular conductance was also attenuated (∼9%). Evidence of increasing noradrenaline spillover (P = 0.09) implicated an elevation in sympathetic outflow in this response. The attenuated femoral blood flow during exercise with fentanyl was associated with a 17% reduction in leg O 2 delivery (P < 0.01) and a concomitant rise in the arteriovenous O 2 difference (4-9%), but leg O 2 consumption remained 7-13% lower than control (P < 0.05). Our findings reveal an essential contribution of continuous muscle afferent feedback to ensure the appropriate haemodynamic and ultimately metabolic response to rhythmic exercise in humans. Abbreviations FBF, femoral blood flow; HR, heart rate; LVC, leg vascular conductance; MAP, mean arterial pressure; NA, noradrenaline; SV, stroke volume.

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Section: Experimental Use Of Intrathecal Fentanylmentioning

confidence: 99%

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

Amann

Runnels

Morgan

et al. 2011

The Journal of Physiology

140

158

View full text Add to dashboard Cite

show abstract

“…Controversy exists regarding the extent of the rostral movement of fentanyl within the CSF following lumbar intrathecal injection (Gourlay et al 1989;Hill & Kaufman, 1990;Ummenhofer et al 2000;Swenson et al 2001) and the diffusion of the drug from the subarachnoid application site into systemic blood (Ummenhofer et al 2000). A cephalad movement of fentanyl within the CSF to or beyond the brainstem, or passage of fentanyl to the systemic circulation and then across the blood-brain barrier (Scott et al 1991) could have annihilated the significance of our findings, since a direct effect of the drug on the brain has been shown to affect intracortical circuits (Vogt et al 1995).…”

Section: Did Lumbar Intrathecal Fentanyl Migrate To Affect Brain Opiomentioning

confidence: 99%

Spinal opioid receptor-sensitive muscle afferents contribute to the fatigue-induced increase in intracortical inhibition in healthy humans

Hilty

Lutz

Maurer

et al. 2011

Experimental Physiology

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We investigated the influence of spinal opioid receptor-sensitive muscle afferents on cortical changes following fatiguing unilateral knee-extensor exercise. On separate days, seven subjects performed an identical five sets of intermittent isometric right-quadriceps contractions, each consisting of eight submaximal contractions [63 ± 7% maximal voluntary contraction (MVC)] and one MVC. The exercise was performed following either lumbar interspinous saline injection or lumbar intrathecal fentanyl injection blocking the central projection of spinal opioid receptor-sensitive lower limb muscle afferents. To quantify exercise-induced peripheral fatigue, quadriceps twitch force (Q tw,pot ) was assessed via supramaximal magnetic femoral nerve stimulation before and after exercise. Motor evoked potentials and cortical silent periods (CSPs) were evaluated via transcranial magnetic stimulation of the motor cortex during a 3% MVC pre-activation period immediately following exercise. End-exercise quadriceps fatigue was significant and similar in both conditions ( Q tw,pot −35 and −39% for placebo and fentanyl, respectively; P = 0.38). Immediately following exercise on both days, motor evoked potentials were similar to those obtained prior to exercise. Compared with pre-exercise baseline, CSP in the placebo trial was 21 ± 5% longer postexercise (P < 0.01). In contrast, CSP following the fentanyl trial was not significantly prolonged compared with the pre-exercise baseline (6 ± 4%). Our findings suggest that the central effects of spinal opioid receptor-sensitive muscle afferents might facilitate the fatigue-induced increase in CSP. Furthermore, since the CSP is thought to reflect inhibitory intracortical interneuron activity, which may contribute to central fatigue, our findings imply that spinal opioid receptor-sensitive muscle afferents might influence central fatigue by facilitating intracortical inhibition.

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“…It has been estimated that morphine administered to the lumbar cistern reaches the cisterna magna in 1-2 hours and the 4 th and lateral ventricles in 3-6 hours [20].…”

Section: Intradural Diffusionmentioning

confidence: 99%

“…Moreover, though to a lesser extent, distribution also occurs via the CSF, traces of opioids, even sufentanil [20], having been found in the cisterna magna only 30 minutes after lumbar intrathecal administration. Fentanyl has been found to reach a maximum cervical CSF concentration as early as 10 minutes after lumbar epidural administration and average 10% of the peak lumbar CSF concentrations, with considerable individual variability [21].…”

Section: Intradural Diffusionmentioning

confidence: 99%

“…We should also ascertain what fraction of the analgesic effect can be attributed to a spinal action and what to a supraspinal action (higher for fentanyl and sufentanil), as well as whether the latter is necessary for the overall effect. It´s has been calculated that less than 5% from epidural morphine, administered as a bolus, can reach medular opioid biophase [9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Intradural Diffusionmentioning

confidence: 99%

See 1 more Smart Citation

Physiology of Spinal Opioids and its relevance for Pain Management Selection

Bujedo¹

2017

Open J Pain Med

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The Effect of Distance From Injection Site to the Brainstem Using Spinal Sufentanil

Cited by 28 publications

References 16 publications

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

On the contribution of group III and IV muscle afferents to the circulatory response to rhythmic exercise in humans

Spinal opioid receptor-sensitive muscle afferents contribute to the fatigue-induced increase in intracortical inhibition in healthy humans

Physiology of Spinal Opioids and its relevance for Pain Management Selection

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