Polyanalgesic Consensus Conference 2007: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

Deer, Timothy R.; Krames, Elliot S.; Hassenbusch, Samuel J.; Burton, Allen W.; Caraway, David; DuPen, Stuart; Eisenach, James C.; Erdek, Michael; Grigsby, Eric; Kim, Philip; Levy, Robert M.; McDowell, Gladstone; Mekhail, Nagy; Panchal, Sunil J.; Prager, Joshua P.; Rauck, Richard; Saulino, Michael; Sitzman, Todd B.; Staats, Peter S.; Stanton‐Hicks, Michael; Stearns, Lisa; Willis, K. Dean; Witt, William; Follett, Kenneth A.; Huntoon, Marc A.; Liem, Leong; Rathmell, James P.; Wallace, Mark; Buchser, Eric; Cousins, Michael J.; Donck, Anne Ver

doi:10.1111/j.1525-1403.2007.00128.x

Cited by 218 publications

(250 citation statements)

References 185 publications

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“…26 An increasing number of papers describe safe administration of long-term intrathecal hydromorphone for chronic pain, 26,27 and hydromorphone is now listed with morphine as a first-line agent for intrathecal administration in chronic pain patients. 28 The current study is limited by a number of factors. The small sample size resulted in an imprecise estimate of the treatment effect; hence, no definitive conclusion can be drawn.…”

Section: Discussionmentioning

confidence: 99%

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

Mhyre

Hong

Greenfield

et al. 2013

Can J Anesth/J Can Anesth

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Purpose Neuraxial hydromorphone has been reported to provide rapid onset of labour analgesia, effective segmental pain relief, and a longer duration of action than commonly used lipophilic opioids. This study was conducted to test the hypothesis that intrathecal hydromorphone reduces the dose requirement for intrathecal bupivacaine to induce rapid analgesia for women in the first stage of labour. Methods In this double-blind randomized controlled sequential allocation trial, 88 labouring parturients received combined spinal-epidural analgesia at 2-6 cm cervical dilation. Participants received intrathecal bupivacaine alone or bupivacaine plus hydromorphone 100 lg with the bupivacaine dose determined using updown sequential allocation. An effective dose was defined as a visual analogue pain score of B10 mm (on a 100-mm pain scale) reported within 20 min of injection. The median effective doses were calculated using the formula of Dixon and Massey and verified using isotonic regression. Results A decrease was observed in the median local analgesic doses (effective dose [ED50]) estimated according to the formulas of Dixon and Massey, with a between-group difference of -0.45 mg. The precision of the estimate was wide-ranging (95% confidence interval -1.23 to 0.33), so no definitive conclusion can be drawn. Conclusion Further research is needed to determine whether or not intrathecal hydromorphone 100 lg changes the dose of intrathecal bupivacaine required to induce labour analgesia within 20 min. Trial registration The trial was conducted in 2007 prior to widespread acceptance of the standard for clinical trial registration. RésuméObjectif Il a été décrit que l'hydromorphone administrée par voie neuraxiale favorisait l'installation rapide de

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Section: Discussionmentioning

confidence: 99%

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

Mhyre

Hong

Greenfield

et al. 2013

Can J Anesth/J Can Anesth

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“…Preclinical studies have typically shown minimal effects upon acute nociception at sub-motor impairing doses of conventional sodium channel blockers given intrathecally. However, they are reported to reliably result in a remarkable analgesic synergy with intrathecal agents such as opiates or alpha 2 agonists with minimal attendant effects upon motor function in animal models [111][112][113][114] and in humans [115][116][117]. There is a clinical literature that suggests that neuraxial local anesthetics may display a tachyphylaxis with chronic exposure that may respond to different local anesthetics [118].…”

Section: Spinal Antagonistsmentioning

confidence: 99%

“…This use of high concentrations in human pumps has led to local toxicity. For opiates, the manifestation of this toxicity is the intrathecal granuloma [37, 116,[461][462][463]. Our group showed that the primary determinant for intrathecal opiate granulomas is the local concentration to which the tissue adjacent to the catheter tip is exposed [49, 51, 52].…”

Section: Drug Dosingmentioning

confidence: 99%

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

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

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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; ...

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“…Despite the wide use of other opioids, local anaesthetics, or clonidine, the place of morphine as the first choice ITA-drug was never really challenged before the apparition of the non-opioid ziconotide (Prialt®), which in 2007 was upgraded to a first-line ITA-drug by the Polyanalgesic Consensus Conference [66,70]. Ziconotide and morphine are the only analgesics approved for ITA by the Food and Drug Administration [132].…”

Section: Ziconotidementioning

confidence: 99%

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

Bäckryd¹

2015

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The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain. In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question. In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor. In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses

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Polyanalgesic Consensus Conference 2007: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

Cited by 218 publications

References 185 publications

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

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

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

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