Epidural Epinephrine and Clonidine

Background It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. Methods Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. Results Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. Conclusions Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.

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Analgesic Efficacy of Peripheral κ-Opioid Receptor Agonist CR665 Compared to Oxycodone in a Multi-modal, Multi-tissue Experimental Human Pain Model

Anesthesiology ◽

10.1097/aln.0b013e3181af6356 ◽

2009 ◽

Vol 111 (3) ◽

pp. 616-624 ◽

Cited By ~ 65

Author(s):

Lars Arendt-Nielsen ◽

Anne E. Olesen ◽

Camilla Staahl ◽

Frédérique Menzaghi ◽

Sherron Kell ◽

...

Keyword(s):

Opioid Receptor ◽

Receptor Agonist ◽

Visceral Pain ◽

Cuff Pressure ◽

Pain Tolerance ◽

Thermal Stimulation ◽

Pain Rating ◽

Pressure Pain ◽

Opioid Receptor Agonist ◽

Stimulation Of

Background Peripherally selective opioids may be beneficial in visceral pain management due to absence of centrally mediated side effects. The objectives of this study were: (1) to assess the effects of a peripherally selective tetrapeptide kappa-opioid receptor agonist, CR665, on experimental pain from multi-modal stimulation of skin, muscle, and viscera, and (2) contrast these effects with those of oxycodone (centrally acting opioid). Methods The study was designed as a single-center, single-dose, randomized, double-blind, placebo and active-controlled, double-dummy, three-way, crossover study in healthy males. Subjects received the following treatments in randomized order: (1) CR665 (0.36 mg/kg) administered intravenously over 1 h, (2) oxycodone (15 mg) administered orally, and (3) placebo administered intravenously and orally. The following pain tests were used: (1) cutaneous pinch pain tolerance threshold, (2) pressure pain detection and tolerance thresholds, (3) cuff pressure pain tolerance threshold, and (4) pain rating thresholds to distension and thermal stimulation of the esophagus. Measurements were performed before dosing and at 30, 60, and 90 min after dosing. Results Compared to placebo, oxycodone elevated cutaneous pinch pain tolerance (P < 0.001) and cuff pressure pain tolerance threshold (P < 0.001), as well as pain rating thresholds (visual analogue scale = 7) to esophageal distension (P < 0.001) and thermal stimulation (P < 0.002). Compared to placebo, CR665 significantly increased the pain rating threshold to esophageal distension (P < 0.005) but reduced the pain tolerance threshold to skin pinching (P = 0.007). Conclusion CR665 had a selective effect on visceral pain. Oxycodone exhibited a generalized effect, elevating thresholds for cutaneous, deep somatic, and visceral pain stimulation.

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Human intracranially-recorded cortical responses evoked by painful electrical stimulation of the sural nerve

NeuroImage ◽

10.1016/j.neuroimage.2006.09.021 ◽

2007 ◽

Vol 34 (2) ◽

pp. 743-763 ◽

Cited By ~ 31

Author(s):

R. Dowman ◽

T. Darcey ◽

H. Barkan ◽

V. Thadani ◽

D. Roberts

Keyword(s):

Electrical Stimulation ◽

Sural Nerve ◽

Cortical Responses ◽

Stimulation Of

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Electrical Stimulation for Immune Modulation in Cancer Treatments

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.795300 ◽

2022 ◽

Vol 9 ◽

Author(s):

Ritopa Das ◽

Sofia Langou ◽

Thinh T. Le ◽

Pooja Prasad ◽

Feng Lin ◽

...

Keyword(s):

Electrical Stimulation ◽

Immune System ◽

Immune Modulation ◽

Cancer Treatments ◽

Different Types ◽

Specific Antigens ◽

High Doses ◽

T Cell Transfer ◽

Deficient Mice ◽

Stimulation Of

Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.

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The Activity of Single Motor Fibres in Arthropods I. The Dragonfly Nymph

Journal of Experimental Biology ◽

10.1242/jeb.42.3.447 ◽

1965 ◽

Vol 42 (3) ◽

pp. 447-461

Author(s):

ANN KNIGHTS

Keyword(s):

Electrical Stimulation ◽

Temporal Summation ◽

Reciprocal Relationship ◽

Response Patterns ◽

Insect Muscle ◽

Frequency Sensitivity ◽

Single Motor ◽

Dragonfly Nymph ◽

Central Inhibition ◽

Stimulation Of

1. Responses to mechanical and electrical stimulation have been investigated in single motor fibres dissected in the segmental nerves of the dragonfly nymph. 2. A large proportion of fibres possessed a background discharge which was often accelerated of inhibited on stimulation. Examples of central inhibition were common. 3. Efferent responses varied in type, delay and regularity, both with the input under stimulation and with the frequency and intensity of the volley. The majority of fibres responded to stimulation of more than one nerve root. 4. In many motor fibres changes in the parameters of stimulation demonstrated a reciprocal relationship between and frequency. An enhanced responsiveness occurred with frequency increases in the range of 10-100/sec. indicatind a considerable importance of temporal summation/facilitation. 5. The characteristic frequency-sensitivity of motor fibres and the variability of their response patterns are discussed in relation to the control of insect muscle.

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Analgesia to pressure–pain develops in the ipsilateral forehead after high- and low-frequency electrical stimulation of the forearm

Experimental Brain Research ◽

10.1007/s00221-013-3776-x ◽

2013 ◽

Vol 232 (2) ◽

pp. 685-693 ◽

Cited By ~ 6

Author(s):

Lechi Vo ◽

Peter D. Drummond

Keyword(s):

Electrical Stimulation ◽

Low Frequency ◽

Pressure Pain ◽

Stimulation Of

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Propofol Suppresses Synaptic Responsiveness of Somatosensory Relay Neurons to Excitatory Input by Potentiating GABAA Receptor Chloride Channels

Molecular Pain ◽

10.1186/1744-8069-1-2 ◽

2005 ◽

Vol 1 ◽

pp. 1744-8069-1-2 ◽

Cited By ~ 28

Author(s):

Shui-Wang Ying ◽

Peter A Goldstein

Keyword(s):

Electrical Stimulation ◽

Chloride Channel ◽

Temporal Summation ◽

Brain Slices ◽

Excitatory Input ◽

Dependent Manner ◽

Sensory Stimuli ◽

Shunting Inhibition ◽

Stimulation Of ◽

Relay Neurons

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 μM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABAA receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.

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Paradoxical differences in pain ratings of the same stimulus intensity

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2017.04.047 ◽

2017 ◽

Vol 16 (1) ◽

pp. 181-181

Author(s):

M.E. McPhee ◽

K.K. Petersen ◽

M.S. Hoegh ◽

T. Graven-Nielsen

Keyword(s):

Stimulus Intensity ◽

Analogue Scale ◽

Temporal Summation ◽

Pain Tolerance ◽

Pain Rating ◽

Baseline Assessment ◽

Identical Stimulus ◽

Pain Ratings ◽

Pain Detection ◽

Stimulation Paradigm

Abstract Aims Stimulus intensity used for assessing temporal summation of pain (TSP) is commonly set at the participants’ pain tolerance. Yet pain ratings during TSP rarely reach that initial pain tolerance pain rating. This study aimed to explore the differences between baseline pain tolerance assessed by cuff algometry and subsequent pain ratings of the same stimulus intensity, and the reliability of these ratings over 2 sessions. Methods In two sessions, separated by one week, 24 healthy, pain-free males had their pressure pain detection (PDT) and tolerance threshold (PTT) recorded using a staircase inflation paradigm (5 kPa increments, 1sec-ON:4sec-OFF) with a cuff algometry system. The pain intensity was assessed during cuff stimulation using an electronic visual analogue scale (VAS, 0–10 cm). Three different inflation paradigms were then performed, using the PTT level as stimulation intensity, and a 1-s duration for each stimulus: PEAKS: 3 inflations at 0.17 Hz, SLOW: 10 inflations at 0.01 Hz, FAST: 10 inflations at 0.5 Hz). Approximately 5-min was kept between the staircase assessment and the first stimulation paradigm, and between each of the 3 inflation paradigms. The PTT and first inflation VAS rating from each paradigm was extracted. Results The VAS rating of PTT pressure was higher in the staircase (VAS: 8.5±2.1 cm) than the first PPT stimulus in any other paradigm (PEAKS: 5.4±2.0; SLOW: 4.6±2.1; FAST: 4.0±2.3, P < 0.05). VAS ratings were also lower in each subsequent paradigm (i.e. PEAKS > SLOW > FAST, P < 0.05). Intra-class coefficients demonstrated excellent reliability for each paradigm (all ICC > 0.79) between sessions. Conclusions PTT, as assessed with the staircase inflation paradigm, was rated more painful during baseline assessment than when the identical stimulus profile (PPT intensity for 1-s) was applied afterwards and this finding is considered reliable.

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Human intracranially recorded cortical responses evoked by painful electrical stimulation of the sural nerve

Acute Pain ◽

10.1016/j.acpain.2007.02.011 ◽

2007 ◽

Vol 9 (1) ◽

pp. 47

Author(s):

R. Dowman ◽

T. Darcey ◽

H. Barkan ◽

V. Thadani ◽

D. Roberts

Keyword(s):

Electrical Stimulation ◽

Sural Nerve ◽

Cortical Responses ◽

Stimulation Of

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Central inhibition of pain is augmented in women with self-injurious behavior

10.1101/2021.05.12.21257091 ◽

2021 ◽

Author(s):

Maria Lalouni ◽

Jens Fust ◽

Johan Bjureberg ◽

Granit Kastrati ◽

Robin Fondberg ◽

...

Keyword(s):

Temporal Summation ◽

Pain Modulation ◽

Pain Tolerance ◽

Conditioned Pain Modulation ◽

Heat Pain ◽

Healthy Controls ◽

Down Regulation ◽

Pain Thresholds ◽

Pressure Pain ◽

Pressure Pain Thresholds

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated higher pain thresholds and tolerance compared with individuals without NSSI. The objective of the study was to assess which aspects of the pain regulatory system that account for this augmented pain perception. In a cross-sectional design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Thermal pain stimuli were assessed during fMRI scanning and NSSI behaviors and clinical symptoms were self-assessed. NSSI participants demonstrated higher pain thresholds during heat and pressure pain compared to controls. During conditioned pain modulation, NSSI participants showed a more effective central down-regulation of pain for NSSI participants. Temporal summation did not differ between the groups. There were no correlations between pain outcomes and NSSI behaviors or clinical characteristics. The fMRI analyses revealed increased activity in the primary and secondary somatosensory cortex in NSSI participants, compared to healthy controls, which are brain regions implicated in sensory aspects of pain processing. The findings suggest segregated inhibitory mechanisms for pain and emotion in NSSI, as pain insensitivity was linked to enhanced inhibitory control of pain in spite of significant impairments in emotion regulation. This may represent an endophenotype associated with a greater risk for developing self-injurious behavior.

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