Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942002000500014
Brazilian Journal of Anesthesiology
Review Article

Uso de medicações por via subaracnóidea no tratamento da dor crônica

Intrathecal drugs for chronic pain control

Anita Perpétua Carvalho Rocha; Lino Lemonica; Guilherme Antônio Moreira de Barros

Downloads: 0
Views: 835

Resumo

JUSTIFICATIVA E OBJETIVOS: A dor crônica é um desafio para a Medicina atual. Novos métodos e medicamentos têm sido propostos com o intuito de controlar os sintomas álgicos. A via de administração subaracnóidea tem se mostrado como uma alternativa viável e segura, embora necessite continuamente ser objeto de estudo de muitos pesquisadores. O objetivo deste trabalho é fazer uma revisão dos medicamentos disponíveis no arsenal terapêutico já consagrados pelo uso e os que se mostram promissores na atualidade para a prática clínica diária. CONTEÚDO: Nesta revisão são avaliados vários fármacos que apresentam ação analgésica quando utilizada via neuroeixo. Opióides, anestésicos locais, agonistas alfa2-adrenérgicos, antagonistas dos aminoácidos excitatórios e inibitórios, acetilcolina, inibidores da acetilcolinesterase, bloqueadores dos canais de cálcio, adenosina, serotonina, antidepressivos tricíclicos e inibidores da síntese de prostaglandinas são analisados no que concerne aos seus efeitos farmacológicos, incluindo os indesejáveis. CONCLUSÕES: Muitos avanços foram registrados no controle dos sintomas álgicos após a utilização das substâncias citadas por via raquidiana, onde certamente algumas serão aproveitadas e enriquecerão o arsenal terapêutico e outras relegadas temporária ou definitivamente. Entretanto, ainda serão necessários muitos estudos clínicos e experimentais para que estes conhecimentos possam ser incorporados e utilizados com segurança pelos profissionais que lidam com o tratamento da dor crônica.

Palavras-chave

DOR, TÉCNICAS ANESTÉSICAS, TÉCNICAS ANESTÉSICAS

Abstract

BACKGROUND AND OBJECTIVES: Chronic pain is a challenge for modern medicine. New methods and drugs have been proposed to control pain. Intrathecal administration is a feasible and safe option, but still requires further investigations. This study aimed at reviewing available and well established drugs as well as new promising alternatives for the daily practice. CONTENTS: Several neuraxial drugs with analgesic action are reviewed. Desirable and undesirable effects of opioids, local anesthetics, alpha2-agonists, excitatory and inhibitory aminoacid antagonists, acetylcholine, acetyl-cholinesterase inhibitors, calcium channel blockers, adenosine, serotonin, tricyclic antidepressants and prostaglandin synthesis inhibitors are analyzed. CONCLUSIONS: Several advances were achieved in controlling pain with intrathecal administration of the above-mentioned drugs. Certainly some will be used, thus enriching therapeutic armamentarium, and others will be temporarily or permanently abandoned. However, several clinical and experimental studies will still be needed for knew knowledge to be incorporated and safely used by professionals dealing with chronic pain.

Keywords

ANESTHETIC TECHNIQUES, ANESTHETIC TECHNIQUES, PAIN

References

Dougherty P, Staats P. Intrathecal drug therapy for chronic pain: rom basic science to clinical practice. Anesthesiology. 1999;91:1891-2026.

Mark CR. Princípios e Prática de Anestesiologia. 1996:1060-1073.

José Jr OO. Opiáceos: O Estado D’arte. 2001:17-18.

Alan NS. Clínica Cirúrgica da América do Norte: Controle da Dor no Período Perioperatório. 1999;79:233-250.

Renê C. Dor Mecanismos e Tratamento. 1999:103-112.

Shertter Ag, Hadley MN, Wilkinson E. Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain. Neurosurgery. 1986;18:740-747.

Auld AW, Maki-Jokela A, Murdoh DM. Intraspinal narcotic analgesia in the treatment of chronic pain. Spine. 1985;10:777-781.

Krames ES, Gershow J, Glassberg A. Continuos infusion of spinally administered narcotics for the relief of pain due to malignant disorders. Cancer. 1985;56:696-702.

Houweling Pl, Ionescu TI, Braams R. Hormonal and pharmacokinetics after intradural (spinal) morphine and general anaesthesia for abdominal aortic surgery. Clinical Drug Investigation. 1999;17:1173-2563.

Young ER, Mackenzie TA. The pharmacology of local anesthetics: A review of the literature. J. Can Dent Assoc. 1992;58:34-42.

Maves TJ, Gebhart GF. Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat. Anesthesiology. 1992;76:91-99.

Chaplan SR, Bach FW, Shafer SL. Prolonged alleviation of tactile allodynia by intravenous lidocaine in neuropathic rats. Anesthesiology. 1995;83:775-785.

Lou L, Wiesenfeld-Hallin Z. Effects of intrathecal local anesthetics on spinal excitability and on the development of autonomy. Pain. 1995;63:173-179.

Barash . Refresher Course in Anesthesiology. JB Lippincott Company. 1993;21:241-254.

Covino BG. General considerations, toxicity and complications of local anesthesia in nimmo. Blackwell Scientific Publications. 1990;11:1033-1034.

Stoetting RK. Local Anesthetic. 1987:148-168.

Backonja MM. Adjuvant analgesic in pain management: iii local anesthetics as adjuvant analgesics. J. Pain Symptom Manage. 1994;9:491-499.

Tamsen A, Gordh T. Epidural clonidine produces analgesia. Lancet. 1984;2:231-232.

Bonnet F, Boico O, Rostaing S. Clonidine-induced analgesia analgesia in postoperative patients: epidural versus intramuscular administration. Anesthesiology. 1990;72:423-427.

Filos KS, Goudas LC, Patroni O. Intrathecal clonidine as a sole analgesic for pain relief after cesarean section. Anesthesiology. 1992;77:267-274.

De Kock M, Crochet B, Morimont C. Intravenous or epidural clonidine for intra and postoperative analgesia. Anesthesiology. 1993;79:525-531.

James CE, Marc DK, Walter K. Alphalpha2-adrenergic agonist for regional anesthesia. Anesthesiology. 1996;85:655-674.

Eisenach JC, Hood DD, Curry R. Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. Pain. 2000;84:57-64.

Liu N. Partial reversal of the effects of extradural clonidine by oral yohimbine in postoperative patients. Br J Anaesth. 1993;70:515-518.

Gordh Jr T, Jansson I, Hartoig P. Interaction between noradrenergic and cholinergic mechanisms involved in spinal nociceptive processing. Acta Anaesthesiol Scand. 1989;33:39-47.

Hood DD, Eisenach JC, Tuttle R. The analgesic interaction between intrathecal neostigmina and epidural clonidine in humans. Anesthesiology. 1985;5:2359-2364.

Hood DD, Mallak KA, Eisenach JC. Interaction between intrathecal neostigmina and epidural clonidine in humans volunteers. Anesthesiology. 1996;85:315-325.

Klimscha W, Tong C, Tommasi E. Intrathecal clonidine and dexmedetomidine stimulate acetylcholine release from spinal cord dorsal horn in sheep: an in vivo microdialysis study. Anesthesiology. 1995;83:A793.

Detweiler DJ, Eisenach JC, Tong C. A cholinergic interaction in alpha 2 adrenoceptor-mediated antinociception in sheep. J Pharmacol Exp Ther. 1993;265:536-542.

Chiari A, Eisenach JC. Spinal anaesthesia: mechanisms, agents, methods, and safety. Reg Anesth Pain Med. 1998;23:357-362.

Dahlstrom A, Fuxe K. Evidence for the existence of monoamine neurons in the central nervous system: II. Experimentalmentally induced changes in the intra-neural amine levels of bulbospinalneuron systems. Acta Physiol Scand. 1965;64:1-36.

Dekock M, Gautier PE, Lavand’hommem P. Intrathecal ropivacaine and clonidine for ambulatory knee arthroscopy: a dose response study. Anesthesiology. 1999;90:710-717.

Rauck RL, Eisenach JC, Jackson K. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1996;94:873-881.

Staats PS, Mitchell VD. Progress in anesthesiology: Future directions for intrathecal therapies. Interv Pain Manag. 2000:1-27.

Melzack R, Wall PD. Textbook of Pain. 1994:1025-1033.

Cotman CW, Monaghan DT. Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Ann Rev Neurosci. 1988;11:61-80.

Champman V, Dickenson AH. The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn. Brain Res. 1992;573:321-323.

Ma QP, Woolf C. Noxious stimuli induce an N-methyl-D- aspartate receptor dependent hypersensitivity of the flexion withdrawal reflex to touch: implications for the treatment of mechanical allodynia. Pain. 1995;61:383-390.

Yamamoto T, Yaksh TL. Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve: Excitatory amino acid antagonists. Pain. 1992;49:121-128.

Yang CY, Wong CS. Intrathecal ketamine reduces morphine requirements in patients with terminal cancer pain. Can J Anaesth. 1996;43:379-383.

Raeder JC, Stenseth LB. Ketamine: a new lock at an old drug. Current Opinion in Anaesthesiology. 2000;13:463-468.

Aprison MH, Shank RP, Davidoff RA. A comparison of the concentration of glycine, a transmitter suspect, in different areas of the brain and spinal cord in seven different vertebrates. Comp Biochem Physiol. 1969;28:1345-1355.

Rizzoli AA. Distribution of glutamic acid, aspartic acid, gamma-aminobutyric acid and glycine in six areas os cat spinal cord before and after transection. Brain Res. 1968;11:11-18.

Bowery N. GABAb receptors and their significance in mammalian pharmacology. Trens Pharmacol Sci. 1989;10:401-406.

Johnston GAR. GABAa receptor pharmacology. Pharmacol Ther. 1996;69:173-178.

Rabow LE, Russek SJ, Farb DH. From ion currents to genomic analysis: recent advances in GABAa receptor research. Synapse. 1995;21:189-274.

Monaghan DT, Olverman HJ, Nguyen L. Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine. Proc Natl Acad sci USA. 1988;85:9836-9840.

Serrao JM, Marks RL, Morley SJ. Intrathecal midazolam for the treatment os cronic mechanical back pain; a controlled comparison with epidural steroid in a pilot study. Pain. 1992;48:5-12.

Borg PA, Krijnen HJ. Long-term intrathecal administration of midazolam and clonidine. Clin J Pain. 1996;12:63-68.

Valentine JM, Lyons G, Bellamy MC. The effect of intrathecal midazolam on post-operative pain. European J Anesth. 1996;13:589-593.

Taira T, Tanikama H, Iseki H. Spinal intrathecal baclofen suppresses central pain after a stroke. J Neural Neurosurg Psychiatry. 1994;57:381-382.

Herman RM, D’luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions. Clin J Pain. 1992;8:338-345.

Albright AL, Ceervi A, Singletary J. - Intrathecal baclofen for epasticity in cerebral palsy. JAMA. 1991;265:1418-1422.

Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg. 1992;6:115-118.

Parke B, Penn RD, Savoy SM. Functional outcome after delivery of intrathecal baclofen. Arch Phys Med Rehabil. 1989;70:30-32.

Satoh O, Omote K. Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the spinal cord in rats with peripheral mononeuropathy. Brain Res. 1996;728:27-36.

Eisenach JC, Hood DD, Tuttle R. Phase 1 safety assessment of intrathecal neostigmina metyl sulfate in humans. Anesthesio- logy. 1995;82:331-343.

Abram SE, Winnie RP. Intratecal acetyl cholinesterase inhibitors produce analgesia that is synergistic with morphine and clonidine in rats. Anesth Analg. 1995;81:501-507.

Chiari A, Eisenach JC. Spinal anaesthesia: Mechanisms, agents, methods, and safety. Reg Anesth Pain Med. 1998;23:357-362.

Liu SS, Hodgson PS, Moore JM. Dose-response effects of spinal neostigmina added to bupivacaine spinal anesthesia in volunteers. Anesthesiology. 1999;90:710-717.

Eisenach JC, Hood DD, Curry R. Phase I human safety assessment of intrathecal neostigmina containing methyl- and propylparabens. Anesth Analg. 1997;85:842-846.

Pan HL, Song HK, Eisenach JC. Effects of intrathecal neostigmina, bupivacaine, and their combination on sympathetic nerve activity in rats. Anesthesiology. 1998;83:842-846.

Gordh Jr T, Jansson I, Hartvig P. A colinergic interaction in alpha2 adrenoceptor-mediated antinociception. Anesthesiology. 1995;83:793-795.

Lauretti GR, Reis MP. Subarachnoid neostigmina does not affect blood pressure or heart rate during bupivacaine spinal anesthesia. Reg Anesth. 1996;21:586-591.

Malmberg AB, Yaksh TL. Effect of continous intrathecal infusion of 2-conapeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate test in rats. Pain. 1995.

Omote K, Sonoda H. Potentiation of antinociceptive effects of morphine by calcium-channel blockers at teh level of the spinal cord. Anesthesiology. 1993;79:746-752.

Karlsten R, Gordh T, Post C. Local antinociceptive and hyperalgesic effects in the formalin test after periferical administration of adenosine analogues in mice. Pharmacol Toxicol. 1992;70:434-438.

Basbaum AL. Descending control of pain transmission: possible serotonergic-enkephalinergic interactions. Advances in experimental medicine and biology. 1981;133:177-189.

Basbaum AI, Fields HL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol. 1978;4:451-454.

Stamford JA. Descending control of pain. Br J Anaesth. 1995;75:217-227.

Mjellem N, Lund A, Hole K. Different functions of spinal 5-HT 1 A and 5-HT2 receptor subtypes in modulating behavior induced by excitatory amino acid receptor agonists in mice. Brain Research. 1993;626:78-82.

Fozard JR. The enigma variations. Trends Pharmacol Sci. 1987;8:501-506.

Richardson BP, Engel G, Danatsch . Identification os serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature. 1985;31:316-326.

Boireau A, Bordier F, Durand G. The antidepressant metapramine is a low-affinity antagonist at N-methyl-D-aspartic acid receptors. Neuropharmacology. 1996;35:1703-1707.

Watanabe Y, Saito H, Abe K. Tricyclic antidepressants block NMDA receptor-mediated synaptic rsponse and induction of long-term potentiation in rat hippocampal slices. Neuropharmacology. 1993;32:479-486.

Eisenach JC, Gebhart GF. Intrathecal amitriptyline acts as an N-Metil-D-Aspartate receptor antagonis in the presence of inflammatory hyperalgesia in rats. Anesthesiology. 1995;83:1046-1054.

Malberg AB, Yaksh TL. Pharmacology of the spinal action of ketorolac, morphine, ST-91, U504488H and L-PIA on the formalin test and an isobolographic analysis of the NSAID interaction. Anesthesiology. 1993;79:270-281.

Choi Y, Raja SN, Moore LC. Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue. J Neurol Sci. 1996;138:14-20.

Yaksh TL, Malmberg AB. Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. Pain. 1993;54:291-300.

Omoigui S. The Pain Drugs Handbook. 1994:173-262; 296; 302;431.

5dd582a60e88258c2cc8fca8 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections