Efficacy of intrathecal adenosine for postoperative pain relief

Sharma, Monika; Mohta, Medha; Chawla, Rajiv

doi:10.1017/s0265021506000342

Cited by 29 publications

(23 citation statements)

References 17 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Published reports [2,6,7,9–16,] in English were retrieved in a computerized search of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, for the period up to July 2016. The keywords used to search these databases were adenosine, postoperative analgesia and postoperative pain(s), and humans, RCT, and CCT were used as filters.…”

Section: Methodsmentioning

confidence: 99%

“…However, 121 studies were excluded after reviewing the title and abstract as these included duplicated and non-original studies, while two were excluded as they did not meet the inclusion criteria; 11 studies were thus further investigated [2,6,7,9–16]. A total of 448 patients who received ADO infusions and 403 controls were enrolled [2,6,7,9–16]. However, there were 2 studies in which the data were presented as bar graphs, and despite having contacted the corresponding authors, no further information could be obtained[10,11].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Adenosine for postoperative analgesia: A systematic review and meta-analysis

Jin

2017

PLoS ONE

View full text Add to dashboard Cite

PurposePerioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We conducted a meta-analysis of randomized controlled trials evaluating the effect of adenosine on postoperative analgesia.MethodsWe retrieved articles in computerized searches of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, up to July 2016. We used adenosine, postoperative analgesia, and postoperative pain(s) as key words, with humans, RCT, and CCT as filters. Data of eligible studies were extracted, which included pain scores, cumulative opioid consumption, adverse reactions, and vital signs. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed-effects or random-effects models, depending on the heterogeneity of the included trials.ResultsIn total, 757 patients from 9 studies were included. The overall effect of adenosine on postoperative VAS/VRS scores and postoperative opioid consumption was not significantly different from that of controls (P >0.1). The occurrence of PONV and pruritus was not statistically significantly different between an adenosine and nonremifentanil subgroup (P >0.1), but the rate of PONV occurrence was greater in the remifentanil subgroup (P <0.01). Time to first postoperative analgesic requirement in the adenosine group was not significantly difference from that of the saline group (SMD = 0.07, 95%CI: −0.28 to 0.41, P = 0.71); but this occurred significantly later than with remifentanil (SMD = 1.10, 95%CI: 2.48 to 4.06, P < 0.01). Time to hospital discharge was not significantly different between the control and adenosine groups (P = 0.78). The perioperative systolic blood pressure was significantly lower in the adenosine than in the control group in the mannitol subgroup (P < 0.01). The incidence of bradycardia, transient first- degree atrioventricular block, and tachycardia was not significantly different between the adenosine and control groups (P > 0.1).ConclusionAdenosine has no analgesic effect or prophylactic effect against PONV, but reduce systolic blood pressure and heart rates. Adenosine may benefit patients with hypertension, ischemic heart disease, and tachyarrhythmia, thereby improving cardiac function.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Adenosine for postoperative analgesia: A systematic review and meta-analysis

Jin

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Intrathecally administered adenosine lowered allodynia in experimental pain models, 214,215 and in patients suffering from neuropathic pain, 216,217 although negative results have also been reported. 218 Adenosine activates four G-protein-bound receptors: A1, A2A, A2B, A3. 219 A1 receptors, which pre-synaptically inhibit neurotransmitter release and post-synoptically inhibit excitatory transmission, 220,221 are found on dorsal horn neurons and on small-to-medium-sized neurons of the DRG.…”

Section: Survey Of Current Targets Of Pain Therapeuticsmentioning

confidence: 99%

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Knezevic

Yekkirala

Yaksh

2017

Anesthesia &Amp; Analgesia

View full text Add to dashboard Cite

Opioids Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management, has limitations and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of re-enforcing activity in the absence of a pain state. The present work provides a non-exclusive overview of current drug targets and potential future directions of research and development. We discuss channels activators and blockers, including: sodium channel blockers, potassium channel activators and calcium channel blockers; glutamate receptor targeted agents, including: NMDA, AMPA and metabotropic receptors). Further, we discuss therapeutics targeted at GABA, alpha2 adrenergic and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors, and agonists/antagonists of adenosine, purine receptors. And cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of drugable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising pre-clinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans’ targets, which should assist in developing non-addictive analgesics.

show abstract

“…In humans, intrathecal adenosine has been shown to reduce allodynia in experimental pain models [300,301] and in patients with neuropathic pain [302,303]. Negative results with intrathecal adenosine have also been reported [304].…”

Section: Intrathecal Adenosinementioning

confidence: 99%

Current and Future Issues in the development of spinal agents for the management of pain

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

View full text Add to dashboard Cite

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.Keywords: Adenovirus transfection, dorsal horn, neurotoxins, pain pathways, spinal drug delivery, spinal analgesics, toxicity. RATIONALETargeting analgesic drugs for direct spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn. Thus, high intensity (e.g., nociceptive) stimulation activates populations of small primary afferents, generating an intensity-dependent increase in activity of second order dorsal horn projection neurons. This excitation is transmitted through spinofugal projection pathways to higher centers, such as the somatosensory thalamus -somatosensory cortex, and to the medial thalamus -limbic cortices that are respectively believed to underlie the sensory-discriminative and affectivemotivational components of the pain experience [1-3]. The dorsal horn encoding process reflects a remarkable plasticity wherein the input-output function of the spinal dorsal horn is subject to pronounced regulation by local neuronal and nonneuronal circuits as well as supraspinal (bulbospinal) input. Thus, following tissue or nerve injury there is an enhanced neuronal response to moderate or low intensity stimuli, e.g., *Address correspondence to this author at the University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, USA; ...

show abstract

Efficacy of intrathecal adenosine for postoperative pain relief

Abstract: Intrathecal adenosine 1,000 microg is not effective as an analgesic for postoperative pain relief, and there is no pre-emptive effect.

Cited by 29 publications

References 17 publications

Adenosine for postoperative analgesia: A systematic review and meta-analysis

Adenosine for postoperative analgesia: A systematic review and meta-analysis

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Current and Future Issues in the development of spinal agents for the management of pain

Contact Info

Product

Resources

About