Evidence-Based Review of the Literature on Intrathecal Delivery of Pain Medication

Bennett, Gary J.; Serafini, Mario; Burchiel, Kim J.; Buchser, Eric; Classen, Ashley; Deer, Timothy R; Pen, Stuart Du; Ferrante, F. Michael; Hassenbusch, Samuel J.; Lou, Leland; Maeyaert, Jan; Penn, Richard D.; Portenoy, Russell K.; Rauck, Richard; Willis, K. Dean; Yaksh, Tony L.

doi:10.1016/s0885-3924(00)00204-9

Cited by 152 publications

(106 citation statements)

References 297 publications

(190 reference statements)

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“…Given that i.t. administration of opioids is one of the most frequently used methods of analgesia in humans (Dougherty and Staats, 1999;Bennett et al, 2000;Rathmell et al, 2005), it is important to study further the functions of spinal NOP receptors in a primate species. Administration of -opioid receptor agonists by the spinal route has This work was supported by United States Public Health Service Grants DA-000254, DA-013685, NS-038476, and EB-003220.…”

Section: Introductionmentioning

confidence: 99%

“…Given that i.t. administration of opioids is one of the most frequently used methods of analgesia in humans (Dougherty and Staats, 1999;Bennett et al, 2000;Rathmell et al, 2005), it is important to study further the functions of spinal NOP receptors in a primate species. Administration of -opioid receptor agonists by the spinal route has become a more popular approach to treatment of pain during the last 2 decades; however, the most common side effect of spinal morphine administration is pruritus (itch sensation), which sometimes is severe and lessens the value of spinal opioids for pain relief (Cousins and Mather, 1984;Waxler et al, 2005).…”

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confidence: 99%

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Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Ko¹,

Wei²,

Woods³

et al. 2006

J Pharmacol Exp Ther

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Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide that is an endogenous ligand for the N/OFQ peptide (NOP) receptor. The aim of this study was to investigate the behavioral responses of N/OFQ and its major fragment N/OFQ(2-17) in monkeys following i.t. administration. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to quantify the amounts of N/OFQ and N/OFQ(2-17) in the cerebrospinal fluid at specific time points when effects of i.t. N/OFQ were sustained and disappeared. Intrathecal administration of N/OFQ dose dependently (10 -100 nmol) produced long-lasting antinociception against a noxious stimulus, 50°C water, and did not elicit itch/scratching responses in monkeys. Subcutaneous pretreatment with a selective NOP receptor antagonist, (ϩ)J-113397 [(1-[3R,4R)-1-cyclooctymethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3,-dihydro-2H-benzimidazol-2-one] (0.1 mg/kg), completely blocked i.t. N/OFQ (100 nmol)-induced antinociception. In contrast, a classic opioid receptor antagonist, naltrexone (0.01 and 1 mg/kg), failed to reverse i.t. N/OFQ-induced antinociception. MALDI-TOF-MS showed that the amount of N/OFQ(2-17) was 4-fold higher than that of N/OFQ at 1.5 h after i.t. administration of 100 nmol N/OFQ. Intrathecal N/OFQ-induced antinociception disappeared at 4.5 h, which corresponded to nearly undetectable cerebrospinal fluid levels of N/OFQ. No other metabolite of N/OFQ was detected at appreciable levels at either the 1.5-or 4.5-h time points. Although significant amounts of N/OFQ(2-17) were detected at the 1.5-and 4.5-h time points, 100 nmol N/OFQ(2-17) i.t. was inactive in changing the monkeys' nociceptive threshold. These results provide the first functional evidence of spinal N/OFQ-induced antinociception in primates and indicate that activation of spinal NOP receptors may be a potential target for spinal analgesics.The orphan opioid receptor has been identified in several species. It was previously called the ORL1 receptor and is now named the NOP receptor, as the fourth member within the opioid receptor family, by the International Union of Pharmacology (Mollereau et al., 1994;Foord et al., 2005). The sequence of the NOP receptor is closely related to each of the classical, well characterized -, ␦-, and -opioid receptors. However, ligands that bind to these classic opioid receptors do not bind NOP receptors with high affinity (Mollereau et al., 1994). The NOP receptor is widely distributed in the central nervous system, and it may participate in a broad range of behavioral and physiological functions (Neal et al., 1999a,b). Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide at the NOP receptor, inhibits cyclic AMP accumulation and Ca 2ϩ currents and increases K ϩ conductance in neurons, similar to the effects of agonists at the other opioid receptors (Meunier et al., 1995;Reinscheid et al., 1995;Jennings, 2001). These in vitro studies seem to support an inhibitory function of NOP receptor activation at sensory neurons (Stanfa et al., 1996;Hel...

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Section: Introductionmentioning

confidence: 99%

“…Given that i.t. administration of opioids is one of the most frequently used methods of analgesia in humans (Dougherty and Staats, 1999;Bennett et al, 2000;Rathmell et al, 2005), it is important to study further the functions of spinal NOP receptors in a primate species. Administration of -opioid receptor agonists by the spinal route has become a more popular approach to treatment of pain during the last 2 decades; however, the most common side effect of spinal morphine administration is pruritus (itch sensation), which sometimes is severe and lessens the value of spinal opioids for pain relief (Cousins and Mather, 1984;Waxler et al, 2005).…”

mentioning

confidence: 99%

Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Ko¹,

Wei²,

Woods³

et al. 2006

J Pharmacol Exp Ther

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“…Die Labordiagnostik sprach gegen eine Entzündungs-reaktion. Dennoch entschlossen wir uns Insgesamt sind die Erfolgsraten aus den Studien mit höherwertigem Design somit deutlich niedriger als 60-70%, wie es aus retrospektiven Beobachtungsreihen ermittelt wurde [5,24,47]. Die intrathekale Therapie hat also eine hohe initiale Versagerquote.…”

Section: Verlaufunclassified

Neurologische Komplikationen und Wirkverlust unter intrathekaler Schmerztherapie

Kindler

Maier

Kagel

et al. 2005

Schmerz

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In a new guideline issued by the German Association for the Study of Pain, intrathecal opioid therapy is described as proven to be effective with relatively few side effects. We reviewed this statement by analysis of the available literature and critical evaluation of the clinical course in a few of our own patients (n=3). In these cases (as well as in a further eight patients), explantation and a switch to oral opioids led to distinctly better alleviation of pain and abatement of the unwanted effects. The problems we discuss do not appear to be rare instances, but by all means complications that are frequently described. The long-term efficacy of intrathecal opioids has not been adequately verified; moreover, their potency is not high. The frequency of undesired events is comparable to that of oral opioid medication, but serious neurological complications are possible. To avoid dose escalations and to recognize neurological complications in time, diligent monitoring by the surgeon or an experienced pain center is essential.

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“…Sur le plan historique, il n'est jamais inutile de rappeler que la première injection de morphine dans l'espace intrathécal fut réalisée en 1901 [2]. Quelle étrange prémonition avait conduit son auteur a essayer cette technique ?…”

Section: Introductionunclassified

Spinal and epidural analgesia in the management of chronic pain

Meignier¹,

Verleysen-Robin²

2007

Douleur analg.

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La place des techniques d'analgésie périmédullaire dépend grandement de l'expérience des équipes, mais cette méthode analgésique reste globalement insuffisamment pratiquée en France au regard de l'expérience étrangère ; pourtant un choix, voire une sélection rigoureuse des patients, une sélection des produits et des techniques permettent une prise en compte adéquate de nombreuses situations extrêmes tant en douleur cancéreuse que bénigne ; les risques sont connus, identifiés et en large partie prévisibles ; le problème reste toujours celui de l'expérience humaine, de la lourdeur de l'investissement par l'équipe de prise en charge et de difficultés administratives certaines.Abstract: The importance of invasive methods in the treatment of chronic and recurrent debilitating pain remains controversial. Epidural and inthrathecal techniques are offering viable options by providing patients with relief, particularly in the case of pain with multiple manifestations and causal mechanisms, whether resulting from cancers or non-malignant tumours. However, these techniques also require experience and expertise to be safe. They are associated with some risk, which must be assessed and might have economic ramifications. Therefore, it is clear that the decision to use these methods must be based on a rigorous protocol for selecting patients and deciding appropriate analgesics; this requires a truly multidisciplinary medical team. For this reason, these techniques are part of a vast therapeutic reserve we rely on conservatively. They do not offer the best solution, but they can and should contribute to relieving pain in many of these patients.

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Evidence-Based Review of the Literature on Intrathecal Delivery of Pain Medication

Cited by 152 publications

References 297 publications

Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Neurologische Komplikationen und Wirkverlust unter intrathekaler Schmerztherapie

Spinal and epidural analgesia in the management of chronic pain

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