Analgesia Mediated by a Direct Spinal Action of Narcotics

Yaksh, Tony L.; Rudy, Thomas A.

doi:10.1097/00132586-197704000-00009

Cited by 126 publications

(151 citation statements)

References 0 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Since the isolation of opioid receptors in the spinal cord in 1976, intrathecal administration of opioids in patients undergoing surgery has gained wide popularity [78]. For instance, there is now strong evidence that in patients undergoing major abdominal surgery, intrathecal morphine alone significantly decreases pain intensity and opioid requirements postoperatively [57].…”

Section: Introductionmentioning

confidence: 99%

Opioids added to local anesthetics for single-shot intrathecal anesthesia in patients undergoing minor surgery: A meta-analysis of randomized trials

Pöpping

Elia

Marret

et al. 2012

Pain

View full text Add to dashboard Cite

a b s t r a c tOpioids are widely used as additives to local anesthetics for intrathecal anesthesia. Benefit and risk remain unclear. We systematically searched databases and bibliographies to February 2011 for full reports of randomized comparisons of any opioid added to any intrathecal local anesthetic with the local anesthetic alone in adults undergoing surgery (except cesarean section) and receiving single-shot intrathecal anesthesia without general anesthesia. We included 65 trials (3338 patients, 1932 of whom received opioids) published between 1983 and 2010. Morphine (0.05-2 mg) and fentanyl (10-50 lg) added to bupivacaine were the most frequently tested. Duration of postoperative analgesia was prolonged with morphine (weighted mean difference 503 min; 95% confidence interval [CI] 315 to 641) and fentanyl (weighted mean difference 114 min; 95% CI 60 to 168). Morphine decreased the number of patients needing opioid analgesia after surgery and decreased pain intensity to the 12th postoperative hour. Morphine increased the risk of nausea (number needed to harm [NNH] 9.9), vomiting (NNH 10), urinary retention (NNH 6.5), and pruritus (NNH 4.4). Fentanyl increased the risk of pruritus (NNH 3.3). With morphine 0.05 to 0.5 mg, the NNH for respiratory depression varied between 38 and 59 depending on the definition of respiratory depression chosen. With fentanyl 10 to 40 lg, the risk of respiratory depression was not significantly increased. For none of these effects, beneficial or harmful, was there evidence of dose-responsiveness. Consequently, minimal effective doses of intrathecal morphine and fentanyl should be sought. For intrathecal buprenorphine, diamorphine, hydromorphone, meperidine, methadone, pentazocine, sufentanil, and tramadol, there were not enough data to allow for meaningful conclusions.Ó

show abstract

Section: Introductionmentioning

confidence: 99%

Opioids added to local anesthetics for single-shot intrathecal anesthesia in patients undergoing minor surgery: A meta-analysis of randomized trials

Pöpping

Elia

Marret

et al. 2012

Pain

View full text Add to dashboard Cite

show abstract

“…Since in these studies drugs were administered systemically, it was not clear to what extent the effects observed were mediated at supraspinal, rather than spinal, sites. Subsequently, however, there have been various studies in which the intrathecal route of drug administration has been used in chronically-implanted rats (Yaksh & Rudy, 1976) and several such studies have again indicated a markedly lesser effectiveness of c-as compared with p-agonists on thermally evoked reflexes (e.g. Schmauss et al, 1983;Bryant et al, 1983; reviewed by Yaksh & Noueihed, 1985;Millan, 1987).…”

Section: Introductionmentioning

confidence: 99%

Spinal antinociceptive actions of μ‐ and κ‐opioids: the importance of stimulus intensity in determining ‘selectivity’ between reflexes to different modalities of noxious stimulus

Parsons

Headley

1989

British J Pharmacology

View full text Add to dashboard Cite

1In electrophysiological experiments in spinalized rats, y-and K-opioids were tested intravenously on the responses of single motoneurones to electronically controlled, alternating noxious heat and noxious pinch stimuli. The effects of u-and K-opioids were compared with those of the general anaesthetic x-chloralose and the dissociative anaesthetic/PCP ligand ketamine. 2 The K-opioids U-50,488 (0.5-16 mg kg'-i.v.) and tifluadom (0.05-1.6 mg kg-1 i.v.) had very similar actions to the p-opioid fentanyl (0.5-16 pg kg '-i.v.). Thus all three agonists reduced thermal and mechanical nociceptive reflexes in parallel and in a dose-dependent manner, but only so long as neuronal responses to the alternating stimuli elicited similar excitability levels in the neurone under study. Ketamine (0.5-16mgkg-1 i.v.) had similar actions to the opioids whereas a-chloralose (20 mg kg -i.v.) had very little effect on neuronal responsiveness. 3 Apparently 'selective' depressions by both p-and K-opioids could be orchestrated by a deliberate mismatch of the intensities of alternating noxious heat and pinch stimuli; as measured by neuronal firing rate, the weaker of the responses to either type of stimulus was invariably reduced to a greater degree. 4 Similar 'selectivity' could be demonstrated for both p-and K-ligands when the weaker and stronger responses were of the same modality, being applied by the same pincher device but with alternating applied force. 5 It is concluded that the 'selective' spinal actions of K-opioids seen in non-thermal over thermal behavioural models of nociception is likely to be related to the relative intensities, rather than the modalities, of the noxious stimuli used. The validity of the interpretation of results obtained in such behavioural studies is discussed.

show abstract

“…s Also in 1976, Yaksh and Rudy first demonstrated the effectiveness of intrathecal opioids in abolishing experimental pain in an animal model. 6 In 1979, initial reports of intrathecal 7 and epidural s use of morphine in humans appeared in the literature.…”

mentioning

confidence: 99%