Effect Of Intrathecal Clonidine Research Articles

Comparison of Intrathecal Bupivacaine with Clonidine Versus Intrathecal Bupivacaine with Fentanyl for Post-operative Pain Treatment in Lower Limb Procedures

Background: One of the anaesthesiologist's key goals during spinal anaesthesia is to keep the body physiology as close to normal as feasible. As we all know, subarachnoid block causes significant hemodynamic changes, especially in trauma and elderly individuals. Sympathetic nervous system denervation, skeletal muscle weakness, or loss of proprioception are not linked to neuraxial opioids. They primarily operate on the receptors found in the substantia gelatinosa of the spinal cord to exert their synergistic analgesic impact on visceral pain. Opioids and local anaesthetics delivered intrathecally have a powerful synergistic analgesic effect. A 2 adrenergic agonist, Clonidine is sometimes used as a local anaesthetic adjuvant with mixed effects. The effects of intrathecal Clonidine vs Fentanyl with 0.5 percent hyperbaric bupivacaine on postoperative analgesic duration and adverse effects were compared.
 Objectives: The purpose of this study was to compare the efficacy of 0.5 percent hyperbaric bupivacaine with Clonidine (75 gs) vs Fentanyl (25 gs) for spinal anaesthesia in patients undergoing lower limb procedures, as well as the postoperative pain alleviation and adverse effects in both groups.
 Methods: This was a prospective study involving 80 patients who were scheduled for elective lower limb surgery under spinal anaesthesia. The participants were randomly assigned to one of two groups: Group C (15mg 0.5 percent bupivacaine + 75gs Clonidine) or Group F (15mg 0.5 percent bupivacaine + 25gs Fentanyl).
 Results: We discovered a time delay in the start of sensory and motor block in group C after assessing the outcomes of our investigation. Group C's sensory and motor block lasted significantly longer compared to group F. The average duration of analgesia in groups C and F was 234.7529.71 minutes and 170.8732.38 minutes, respectively. Compared to group C, the demand for rescue analgesics was higher in group F throughout 24 hours. Bradycardia affected 12 individuals in group C, while pruritus affected 12 patients in group F. Five of the patients in group F experienced nausea.
 Conclusion: In compared to 25gs Fentanyl, adjuvant use of Clonidine 75gs with hyperbaric bupivacaine prolongs the duration of both sensory and motor blockage, as well as the length of analgesia postoperatively, without generating substantial hemodynamic compromise or other side effects.

Effect of intrathecal clonidine on subarachnoid block characteristics in patients undergoing TURP and TURBT

Effect of intrathecal clonidine on subarachnoid block characteristics in patients undergoing TURP and TURBT

Transdermal nitroglycerine enhances the post-operative analgesic effect of intrathecal clonidine in abdominal hysterectomies

Transdermal nitroglycerine enhances the post-operative analgesic effect of intrathecal clonidine in abdominal hysterectomies

Rewarding Electrical Brain Stimulation in Rats after Peripheral Nerve Injury

Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the abuse liability of commonly abused prescription opioids. Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into the left ventral tegmental area (VTA). Rats were trained to lever press for intracranial electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl, hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second group of neuropathic rats were implanted with intrathecal catheters, and the effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of VTA ICSS were assessed. The effects of electrical stimulation of the VTA on mechanical allodynia were assessed in SNL rats. Responding for VTA ICSS was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a significant facilitation of VTA ICSS in control (maximum shift 24.10 ± 6.19 Hz) but not SNL rats (maximum shift 16.32 ± 7.49 Hz), but also reduced maximal response rates in SNL rats. Intrathecal administration of clonidine, adenosine, and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical stimulation of the VTA did not alter mechanical allodynia following nerve injury. The present data suggests that the positive reinforcing effects of commonly abused prescription opioids are diminished following nerve injury. In addition, alleviation of mechanical allodynia with nonopioid analgesics does not appear to stimulate limbic dopamine pathways originating from the VTA in SNL rats.

Clonidine inhibits itch-related response through stimulation of α 2-adrenoceptors in the spinal cord in mice

The present study investigated whether clonidine – an α 2-adrenoceptor agonist known to relieve pain – is able to suppress itch-related behavior in mice. An intraplantar injection of serotonin induced biting (an itch-related response), which was inhibited by intraperitoneal and intrathecal, but not intraplantar or intracisternal, clonidine injections. The effect of intrathecal clonidine was inhibited by intrathecal injections of phentolamine (a non-selective α-adrenoceptor antagonist) and yohimbine (a selective α 2-adrenoceptor antagonist), but not by prazosin (a selective α 1-adrenoceptor antagonist). The effect of intraperitoneal clonidine was also inhibited by intrathecal yohimbine. These results suggest that clonidine is an effective antipruritic agent and that the effect is mainly mediated by the stimulation of α 2-adrenoceptors in the dorsal horn.

Evaluation of the effect of intrathecal clonidine to decrease shoulder tip pain in laparoscopy under spinal anaesthesia

Sixty ASA grade I/II patients scheduled for elective short laparoscopic procedures under spinal anaesthesia were divided into two groups of 30 each. The first group (group C) received 3.5 ml of hyperbaric bupivacaine with 30 mcg of clonidine. The second group (group B) received plain bupivacaine 3.5 ml. Till date, the limiting factor for use of spinal anaesthesia for laparoscopy was patient’s discomfort due to shoulder tip pain. From our study it can be concluded that bupivacaine along with clonidine in low doses provides good sedation and analgesia in intraoperative and post-operative period and at the same time abolishes shoulder tip pain during laparoscopic procedures. In addition, no significant changes in haemodynamics occur with the low dose of clonidine used.

Activation of Spinal α-2 Adrenoceptors, but Not μ-Opioid Receptors, Reduces the Intrathecal N-Methyl-d-Aspartate-Induced Increase in Spinal NR1 Subunit Phosphorylation and Nociceptive Behaviors in the Rat

A previous study from our laboratories showed that a significant reduction in spinal N-methyl-D-aspartate (NMDA) receptor NR1 subunit phosphorylation (pNR1) is associated with the antiallodynic effect produced by intrathecal (IT) injection of the alpha-2 adrenoceptor agonist, clonidine, in neuropathic rats. In this study, we determined whether the spontaneous pain and increased pNR1 expression induced by NMDA injection are reduced by IT injection of either clonidine or the mu-opioid receptor agonist, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO). We examined the effect of clonidine (20 microg/rat) or DAMGO (1 microg/rat) injection on IT NMDA-induced spontaneous nociceptive behavior and pNR1 expression in the spinal dorsal horn. We also determined whether the effect of clonidine is mediated by alpha-2A or alpha-2C adrenoceptors. Finally, rat spinal cords were immunohistochemically processed for double staining of pNR1 and alpha-2A or alpha-2C adrenoceptors or mu-opioid receptors. The NMDA-induced increase in both pNR1 expression and nociceptive behavior was significantly reduced by IT clonidine but not DAMGO. This analgesic effect of clonidine was blocked by administration of either an alpha-2A (BRL44408, 30 microg/rat) or an alpha-2C (JP-1302, 50 microg/rat) adrenoceptor antagonist. In addition, immunocytochemistry revealed that spinal pNR1 immunoreactive cells co-contain alpha-2A and alpha-2C adrenoceptors. These results demonstrate that the IT NMDA-induced increase in pNR1 expression and nociceptive behavior is significantly reduced by activation of alpha-2 adrenoceptors, but not mu-opioid receptors, in the spinal cord dorsal horn. Furthermore, these findings suggest that the modulation of spinal NR1 phosphorylation is linked to the effect of IT clonidine on postsynaptic neuronal activity.

Effect of intrathecal morphine plus clonidine on expression of protein kinase A catalytic subunit in the spinal dorsal horn in a rat model of incisional pain

Objective To observe the effect of intrathecal clonidine plus morphine on expression of protein kinase A (PKA) catalytic subunit in the spinal dorsal horn in a rat model of incisional pain. Methods Eighty male Sprague-Dawley rats were divided randomly into five groups: sham group, control group, pre-incisional morphine 2.5 μg group, pro-incisional clonidine 5 μg group and preincisional morphine 2.5 μg plus clonidine 5 lag group (n=16). lntrathecal catheter and the model of incisional pain were pro-duced according to Yaksh and Brennan's described method respectively. Changes of pain behavior were assessed by mechanical with-drawal threshold (MWT) and thermal withdrawal latency(TWL). The expressions of PKA catalytic subunit in the spinal dorsal horn were assessed by immunohistochemical method and western blotting analysis. Results Compared with sham group, MWT and TWL in control group were decreased significantly at 2 h after incision (P<0.01) and the number of positive cells and protein expression of PKA catalytic subunit in the spinal dorsal horn were increased significantly in control group (P<0.01). Compared with control group, MWT and TWL in pre-incision morphine 2 μg plus clonidine 5 lag group were increased significantly at 2 h after incision (P<0.01) and the number of positive cells and protein expression of PKA catalytic subunit in the spinal dorsal horn were decreased significantly in pre-incision morphine 2 μg plus clonidine 5 μg group (P<0.01). However, MWT, TWL and the number of positive cells and pro-tein expression of PKA catalytic subunit in the spinal dorsal horn changed with no statistical significance in pre-incisional morphine 2.5 μg group and pre-incisional clonidine 5 μg group compared with control group. Conclusion lntrathecal clonidine significantly enhances the antinociceptive effect of intrathecal morphine in a rat model of incisional pain, which might be associated with inhibi-tion of the increased expression of PKA catalytic subunit in spinal cord. Key words: Pain; Clonidine; Morphine; Protein kinase A; Spinal cord

Intrathecal clonidine suppresses zymosan-induced peripheral leukocyte migration in a mouse air pouch model via activation of spinal muscarinic type 2 receptors and sympathoadrenal medullary activity

These studies were performed to examine the potential anti-inflammatory effect of intrathecal (IT) clonidine (an α 2-adrenoceptor agonist) on zymosan-induced leukocyte migration in a mouse air pouch model. IT clonidine dose-dependently suppressed zymosan-induced leukocyte migration and this effect was blocked by IT idazoxan (an α 2-adrenoceptor antagonist) pretreatment. Since a number of studies have previously shown that spinal α 2-adrenoceptors are functionally associated with spinal cholinergic activity, we next examined whether spinal acetylcholine (ACh) receptors were also involved in mediating this anti-inflammatory effect of IT clonidine. IT pretreatment with atropine (a muscarinic receptor antagonist), but not hexamethonium (a nicotinic receptor antagonist) completely blocked the anti-migratory effect of IT clonidine. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic M 2 antagonist), but not pirenzepine (an M 1 antagonist) or 4-DAMP (an M 3 antagonist), suppressed clonidine's anti-inflammatory effect. Finally, we studied the potential roles of the sympathetic nervous system and the hypothalamo-pituitary–adrenal axis in clonidine's anti-inflammatory effect. Adrenalectomy or systemic injection of propranolol (a β-adrenoceptor antagonist) blocked clonidine's effect. However, pretreatment with RU486 (a corticosteroid antagonist) or peripheral sympathetic denervation using 6-hydroxydopamine had no effect. Furthermore, IT clonidine increased Fos expression in zymosan treated mice exclusively in T7–T11 sympathetic preganglionic neurons (which mainly project to the adrenal medulla), but not those of the T1–T6 or T12–L2 spinal segments. Moreover, IT methoctramine significantly reduced this increase in Fos expression. Collectively, these findings suggest that IT clonidine suppresses peripheral leukocyte migration via a sympathoadrenal medullary pathway, and that this suppressive effect is mediated by spinal M 2 receptors.

The Short-lasting Analgesia and Long-term Antihyperalgesic Effect of Intrathecal Clonidine in Patients Undergoing Colonic Surgery

The Short-lasting Analgesia and Long-term Antihyperalgesic Effect of Intrathecal Clonidine in Patients Undergoing Colonic Surgery

Spinal Muscarinic and Nicotinic Subtypes Activated by Clonidine in Postincisional Pain

A recent model of acute incisional pain has been characterized that strongly parallels the postoperative period in patients experiencing evoked pain. In that setting, abundant literature has revealed antihypersensitive effects produced by intrathecally administered alpha2-adrenergic receptor agonists, such as clonidine, in both animals and humans. Recent reports have suggested an obligatory role of spinal acetylcholine receptors in the analgesic action of intrathecal clonidine. The authors sought to determine the involvement of spinal muscarinic and nicotinic receptor subpopulations in the antihypersensitivity effect of intrathecal clonidine in a rodent model for human postoperative pain. After intrathecal catheterization, rats underwent superficial plantar incision. Clonidine or a combination of clonidine and muscarinic receptor subtype antagonists (M1, M2, M3, and M4) or nicotinic receptor subtype antagonists (alpha4beta2 and alpha7) were intrathecally administered, and withdrawal thresholds to mechanical stimuli were examined. Spinal clonidine maximally reduced hypersensitivity adjacent to the wound 30 min after its injection. When animals were intrathecally pretreated with the M1 muscarinic antagonist toxin MT-7, the M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine, and the M4 muscarinic antagonist toxin MT-3, clonidine lost its antihypersensitive action. When animals were intrathecally pretreated with the alpha4beta2 nicotinic receptor antagonist dihydro-beta-erythroidine, but not with the alpha7 nicotinic receptor antagonist methyllycaconitine, the antihypersensitivity action of clonidine was abolished. These data indicate for the first time that the clonidine-induced increase in punctuate mechanical threshold is mediated via the activation of all but M2 muscarinic receptor subtypes, and via the activation of alpha4beta2 but not alpha7 nicotinic receptor subtypes in a rodent model for human postoperative pain.

Peripheral nerve injury alters the alpha2 adrenoceptor subtype activated by clonidine for analgesia.

Previous studies suggest that the alpha adrenoceptor subtype is the target for spinally administered alpha -adrenergic agonists, clonidine, for pain relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist, induces antinociception, and intrathecally administered alpha antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity. The same mechanical stimulus was applied to normal rats and those following spinal nerve ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal threshold to the stimulus was determined. To further examine subtypes, animals were spinally pretreated with vehicle, BRL 44408 (an alpha subtype-preferring antagonist), and ARC 239 (an alpha subtype-preferring antagonist). In normal animals, clonidine's effect was diminished by pretreatment with either antagonist, whereas ST 91's antinociceptive effect was solely blocked by pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity action of both clonidine and ST 91 was blocked by administration of ARC 239, whereas BRL 44408 was ineffective. These data agree with previous studies supporting that the alpha adrenoceptor is important to the antinociceptive effect of clonidine in normal animals. Nerve injury alters this and results in a total reliance on alpha adrenoceptors.

Antihypersensitivity Effect of Intrathecal Clonidine in a Rat Model of Postoperative Pain: Both a2A and a2NON A Adrenoceptors Participate

Antihypersensitivity Effect of Intrathecal Clonidine in a Rat Model of Postoperative Pain: Both a2A and a2NON A Adrenoceptors Participate

Spinal transection increases the potency of clonidine on the tail-flick and hindlimb flexion reflexes

The effect of intrathecal clonidine on thermal nociception and hindlimb flexion was assessed in acute and chronic spinally transected rats. After an acute, 1-day spinalization, there was no change in the antinociceptive dose–response function to clonidine, relative to intact rats. However, there was a significant increase in potency 31 days after spinalization. Low doses of clonidine (0.25, 1, 4 and 20 μg) did not affect the nonnociceptive flexion reflex of acute spinal rats, but they elicited a dose-dependent response in chronic spinal rats. These data provide behavioral evidence of supersensitivity to α-adrenoceptor agonists in chronic spinal rats.

Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain.

A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT) clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and antihyperalgesic effects of IT clonidine were examined post-treatment in a rat model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia. Using a chronic model of spinal cord dialysis, we examined the effect of the adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the development of chronic pain and assessed the antinociceptive effects and mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups receiving IT clonidine in discrete doses of 1, 10 or 50 microg, 3 or 24 hr post-inflammation. Measurement of total NOx (NO + NO2- + NO3-) was used to determine NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed using a radiant heat thermal hyperalgesia model. CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation. A dose-dependent suppression of thermal hyperalgesia and spinal NO release was observed after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain model suggests that clonidine's spinal antihyperalgesic mechanisms act through inhibition of spinal NO release.

Anaesthetic and postoperative analgesic effects of intrathecal clonidine in the transurethral resection of vesical tumours

Anaesthetic and postoperative analgesic effects of intrathecal clonidine in the transurethral resection of vesical tumours

Analgesic and Hemodynamic Effects of Intrathecal Clonidine as the Sole Analgesic Agent During First Stage of Labor: A Dose-Response Study

Analgesic and Hemodynamic Effects of Intrathecal Clonidine as the Sole Analgesic Agent During First Stage of Labor: A Dose-Response Study

Role of spinal NO in the antiallodynic effect of intrathecal clonidine in neuropathic rats

Role of spinal NO in the antiallodynic effect of intrathecal clonidine in neuropathic rats

Effect of Intrathecal Clonidine in Hyperbaric Bupivacaine Spinal Anesthesia

Effect of Intrathecal Clonidine in Hyperbaric Bupivacaine Spinal Anesthesia

Attenuating effects of intrathecal clonidine on the exercise pressor reflex

We tested the hypothesis that intrathecal injection of clonidine, an alpha 2-adrenergic agonist, attenuated the reflex cardiovascular and ventilatory responses to static muscular contraction in cats. Before clonidine (1 microgram in 0.2 ml), contraction-induced reflex increases (n = 10) in mean arterial pressure and ventilation averaged 25 +/- 3 mmHg and 359 +/- 105 ml/min, respectively, whereas after clonidine these increases averaged 8 +/- 4 mmHg and 200 +/- 114 ml/min, respectively (P less than 0.05). Clonidine had no effect on the heart rate response to contraction. Intrathecal injection of yohimbine (10 micrograms; n = 5), an alpha 2-adrenergic antagonist, but not prazosin (10 micrograms; n = 3), an alpha 1-adrenergic antagonist, prevented the attenuating effects of clonidine on the reflex pressor and ventilatory responses to contraction. Our findings were not due to the spread of clonidine to the medulla, because the reflex pressor and ventilatory responses to contraction were not attenuated by injection of clonidine (1 microgram) onto the medulla (n = 3). In addition, our findings were not due to a clonidine-induced withdrawal of sympathetic outflow, because intrathecal injection of clonidine (1 microgram) did not attenuate increases in arterial pressure and ventilation evoked by high-intensity electrical stimulation of the cut central end of the sciatic nerve (n = 5). Furthermore, our findings were not due to a local anesthetic action of clonidine, because application of this agent to the dorsal roots had no effect on the discharge of group IV muscle afferents. We conclude that stimulation of alpha 2-adrenergic receptors in the spinal cord attenuates the reflex pressor and ventilatory responses to static contraction.