Intrathekale und epidurale Applikation von Nichtopioidanalgetika zur Therapie akuter und chronischer Schmerzen
Tóm tắt
Nozizeptive Reize werden im Hinterhorn des Rückenmarks durch verschiedene Rezeptorsysteme moduliert. Hierbei wirken die verschiedenen Systeme entweder unabhängig voneinander, komplementär, additiv oder supraadditiv. Die Systeme sind durch zahlreiche Substanzen, die auf Rückenmarkebene appliziert werden können, stimulierbar. Nichtopioidanalgetika wirken analgetisch, ohne die Motorik zu beeinflussen. Gegenüber spinal applizierten Opioiden besteht eine geringere Gefahr der Atemdepression. Bei der Therapie chronischer Schmerzen können Nichtopioidanalgetika alleine oder in Kombination mit Opioiden eine Alternative bei einer Opioidtoleranz darstellen. Der α2-AdrenozeptoragonistClonidin wirkt bei einer Dosierung von ≥150 μg epidural antinozizeptiv, sowohl bei der Therapie akuter als auch bei der Therapie chronischer Schmerzen. In Kombination mit Opioiden wird die Opioidwirkung synergistisch verstärkt. Die Wirkung von Lokalanästhetika wird durch Zugabe von Clonidin verstärkt und verlängert. Bei bestehender Opioidtoleranz nach chronischer spinaler Opioidapplikation konnte mit Clonidin alleine oder in Kombination mit einem Opioid eine gute Schmerzreduktion nach epiduraler Applikation erreicht werden. Das wasserlösliche BenzodiazepinMidazolam wurde zur Therapie von Karzinomschmerzen, postoperativen Schmerzen, chronischen Rückenschmerzen und zur Therapie einer spinalen Spastik epidural appliziert. Intrathekal appliziertesBaclofen, ein Derivat der g-Aminobuttersäure, hat sich seit Jahren zur Therapie der schweren spinalen Spastik bewährt und kann bei Schmerzen, die durch eine Spastik bedingt sind, indirekt analgetisch wirken. Eine direkte analgetische Wirkung dieser Substanz wurde bisher nicht ausreichend belegt.Calcitonin führt bei alleiniger Applikation oft zu einer unzureichenden Analgesie. Bei Kombination mit Morphin ist eine Reduktion der Morphindosierung möglich. Häufige Nebenwirkungen nach spinaler Applikation sind vor allem Übelkeit und Erbrechen. Intrathekal appliziertesSomatostatin wirkt antinozizeptiv. Bei einigen Tierspezies wirkte Somatostatin in analgetischer Dosierung neurotoxisch. Die Sicherheit der Anwendung bei Menschen ist nicht ausreichend belegt.Ketamin stimuliert auf spinaler Ebene Opioid-, Adreno- und serotoninerge Rezeptoren. Die klinischen Ergebnisse mit spinal appliziertem Ketamin waren jedoch widersprüchlich. Eine Neurotoxizität ist nicht ausgeschlossen.Lysin-Acetylsalicylat (LAS) wurde zur Therapie schwerer chronischer Schmerzen intrathekal appliziert. Bei Karzinomschmerzen und schweren chronischen Rückenschmerzen konnte mit der intrathekalen Gabe dieser Substanz eine Analgesie erreicht werden, die nach einer einmaligen Injektion bis zu 2 Monaten anhielt. In Tierversuchen waren bei Verwendung einer 45%igen Lösung histologische Veränderungen bei 2 Versuchstieren nachweisbar. Aufgrund der guten klinischen Ergebnisse könnte LAS eine Alternative in der Karzinomschmerztherapie vor Durchführung neurodestruktiver Verfahren sein, wenn die Neurotoxizität bei klinisch üblicher Dosierung ausgeschlossen werden kann.
Tài liệu tham khảo
Ackerman E, Chrubrasik J, Weinstock M, Wünsch E (1985) Effect of intrathecal somatostatin on pain threshold in rats. Schmerz-Pain-Douleur 6:41
Amiot JF, Pallaci JH, Pellerin M (1986) Spinal toxity of lysine acetylsalcylat and ketamine hydrochloride given by the intrathecal route in the rat. Ann Fr Anesth Reanim 5:462
Aran S, Proudfit HK (1990) Antinociceptive interactions between intrathecally administered alpha noradrenergic agonists and 5′-N-ethylcarboxamide adenosine. Brain Res 519:287
Blanchard J, Menk EJ, Ramamurthy S, Hoffman J (1988) Subarachnoidal and epidural calcitonin for the management of cancer pain. Anesth Analg 67:S2
Blanchard J, Menk E, Ramamurthy S, Hoffman J (1990) Subarachnoid and epidural calcitonin in patients with pain due to metastatic cancer. J Pain Sympt Management 5:42
Bonnet F, Boico O, Rostaing S, Saada M, Loriferne JF, Touboul C, Abhay K, Ghignone M (1989) Postoperative analgesia with extradural clonidine. Br J Anaesth 63:465
Bonnet F, Boico O, Rostaing S, Liferne JF, Saada M (1990) Clonidine-induced analgesia in postoperative patients: epidural versus intramuscular administration. Anesthesiology 72:423
Bonnet F, Catoire P, Brun Buisson V, Saada M, Francois Y (1990) Effects of oral and subarachnoidal clonidine on spinal anesthesia with bupivacaine. Reg Anesth 15:211
Brock-Utne JG, Rubin J, Mankowitz E (1986) Letters to the editor. Anesth Analg 65:990
Carabine UA, Milligan KR, Moore J (1992) Extradural clonidine and bupivacaine for postoperative analgesia. Br J Anaesth 68:132
Carli P, Ecolley C, Chrubrasik J, Benlabed M, Gross JB, Samii K (1986) Spread of analgesia and ventilatory responses to CO2 following epidural somatostatin. Anesthesiology 65:A216
Chrubrasik J (1985) Zur spinalen Infusion von Opioiden und Somatostatin. Verlag Hygieneplan
Chrubrasik J (1985) Somatostatin: eine Übersicht. Anaesth Intensiv Notfallmed 20:165
Clavier N, Lombard M-C, Besson J-M (1992) Benzodiazepines and pain: effects of midazolam on the activities of nonspecific dorsal horn neurons in the rat spinal cord. Pain 48:61
Clavier N, Lombard M-C, Besson J-M (1990) Benzodiazepines and nociceptive dorsal horn neural activity in the rat spinal cord: antinociceptive or anticonvulsant effects? Pain 5: [Suppl]:224
Cohn ML, Cohn M (1975) Barrel rotation induced by somatostatin in the non lesioned rat. Brain Res 96:138
Coombs DW, Saunders R, Gaylor M, La Chance D, Lawrence J (1984) Clinical trial of intrathecal clonidine for cancer pain. Reg Anesth 9:34
Coombs DW, Saunders RL, LaChance D, Savage S, Ragnarsson TS, Lawrence EJ (1985) Intrathecal morphine tolerance: use of intrathecal clonidine, DADLE, and intraventricular morphine. Anesthesiology 63:358
Coombs DW, Jensen LB, Murphy C (1987) Microdose of intrathecal clonidine and morphine for postoperative analgesia. Anesthesiology 67:A238
Coventry DM, Todd G (1989) Epidural clonidine in lower limb deafferation pain. Anesth Analg 69:424
Cripps TP, Goodchild CS (1988) Intrathecal midazolam and the stress response to upper abdominal surgery. Clin J Pain 4:125
Dalmas TL (1986) Les effect analgésique de la somatostatin. Thèse pour le doctirat en médecine, Université Lille
Dahm LS, Beric A, Dimitrijevic MR, Wall PD (1989) Direct spinal effect of a benzodiazepine (Midazolam) on spasticity in man. Stereotact Funct Neurosurg 53:85
De Castro J, Meynadier J, Zenz M (eds) (1991) Regional analgesia. Kluwer Academic Publishers, Dordrecht Boston London
De Kock M, Martin N, Scholtes JL (1992) Central effects of epidural and intravenous clonidine. Reg Anesth 17 [Suppl]:157
Delauny L, Leppert C, Dechaubry V, Baubillier E, Bonnet F (1991) Epidural clonidine reduces epidural fentanyl requirements and side effects in post-operative patients. Anesthesiology 75:A1086
Devoghel JC (1983) Small intrathecal doses of lysine-acetylsalicylat relief intractable pain in man. J Int Med Res 11:90
Dralle D, Müller H, Zierski J, Klug N (1985) Intrathecal baclofen for spasticity. Lancet II:1003
Dranser K, Fields HL (1988) Synergy between the antinociceptive effects of intrathecal clonidine and systemic morphine in the rat. Pain 32:309
Edwards M, Serrao JM, Gent JP, Goodchild CS (1990) On the mechanism by which midazolam causes spinally mediated analgesia. Anesthesiology 73:273
Eisenach JC, Lysk SZ, Viscomi CM (1989) Epidural clonidine analgesia following surgery: phase I. Anesthesiology 71:640
Eisenach JC, Dewan DM (1990) Intrathecal clonidine in obsterics: sheep studies. Anesthesiology 72:663
Eisenach JC, Tong CT (1991) Site of hemodynamic effects of intrathecal alpha-2-adrenergic agonists. Anesthesiology 74:766
Falke KJ, Chrubrasik J, Vitrac P, Blond S, Meynadier J, Zindler M, Scherpeel P (1986) Effectiveness of spinal salmon calcitonin in acute and chronic pain. II Int Symposium: The Pain Clinic, Lille, France
Ferit PA, Aydinli I, Akra S (1992) Management of cancer pain with epidural clonidine. Reg Anesth 17 [Suppl]:173
Finck AD, Ngai SH (1982) Opiate receptor mediation of ketamine analgesia. Anesthesiology 56:291
Fiore CE, Castorina F, Malatino LS, Tamburino C (1983) Antalgic activity of calcitonin: effectiveness of the epidural and subarachnoidal routes in man. Int J Clin Pharmacol Res 3:257
Fraiolo F, Fabbri A, Gnessi L, Moretti C, Santoro C, Felcici M (1982) Subarachnoidal calcitonin for intolerable pain. Lancet II:831
Fratta W, Casu M, Balestieri A, Loviselle A, Biggio G, Gessa GI (1980) Failure of ketamine to interact with opiate receptores. Eur J Pharmacol 61:389
Gaumann DM, Yaksh TL (1988) Intrathecal somatostatin in rats: antinociception only in presence of toxic effects. Anesthesiology 68:733
Gauman DM, Yaksh TL, Post C Wilcox GL, Rodriguez M (1989) Intrathecal somatostatin in cat and mouse. Studies on pain, motor behavior, and histopathology. Anesth Analg 70:222
Gibson SJ, Polak JM, Bloom SR, Sabate IM, Muldery PM, Ghatei MA (1984) Calcitonin gene-related peptide immunreactivity in the spinal cord of man and eight other species. J Neurosci 4:3101
Glynn C, Dawson D, Sanders R (1988) A double blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. Pain 34:123
Glynn CJ, Jamous MA, Teddy PJ (1992) Cerebrospinal fluid kinetics of epidural clonidine in man. Pain 49:361
Goodchild CS, Serrao JM (1987) Intrathecal midazolam in the rat: evidence for spinal mediated anglesia. Br J Anesth 59:1563
Goodchild CS, Gentt JP, Marks RL, Serrao JM (1989) Inadvertent epidural midazolam and fentanyl. Anaesthesia 44:609
Goodchild CS, Noble J (1987) The effects of intrathecal midazolam on sympathic nervous system reflexes in man—a pilot study. Br J Clin Pharmacol 23:279
Gordh T (1988) Epidural clonidine for treatment of postoperative pain after thoractomy. A double-blind placebocontrolled study. Acta Anesth Scand 32:702
Handwerker HO (1984) Experimentelle Schmerzanalyse beim Menschen. In: Zimmermann M, Handwerker HO (Hrsg) Schmerz. Springer, Berlin Heidelberg New York S 87
Hardy PA, Wells JCD (1988) Pain after spinal intrathecal clonidine. Anesthesia 43:1026
Harfstrand A, Kalia M, Fuxe K, Kaijer L, Agnati LF (1984) Somatostatin induced apnoa: interaction with hypoxia and hypercapnia in rats. Neurosci Lett 50:37
Hoffmann P, Nguyen G, Schürmann C, Schockenhoff B (1989) Klinische Untersuchungen zur epiduralen Anwendung von Clonidin zur postoperativen Analgesie. Anästhesist 38 [Suppl 1]:557
Islas J-A, Astorga J, Laredo M (1985) Epidural ketamine for control of post-operative pain. Anesth Analg 64:1161
Jänig W (1993) Biologie und Pathologie der Schmerzmechanismen. In: Zenz M, Jurna I (Hrsg) Lehrbuch der Schmerztherapie. Wissenschaftlicher Verlag, Stuttgart, S 15
Jaffe S, Harbicek V, Friesen H, Chernick V (1978) Effect of somatostatin and L-glutamate on neurons of the sensimotor cortex in awake habituated rabbits. Brain Res 153:414
Jurna I (1984) Depression of the nociceptive sensory activity in the rat spinal cord due to the intrathecal administration of drugs: effects of diazepam. Neurosurgery 15:917
Jurna I, Spohrer B, Bock R (1992) Intrathecal injection of acetylsalicylic acid, salicylic acid and indomethacin depresses C-evoked activity in the rat thalamus and spinal cord. Pain 49:249
Kalia M, Fuxe K, Agnati LF, Härfstrand A (1984) Somatostatin produces apnea and is localized in medullary respiratory nuclei: a possible role in apneic syndromes. Brain Res 296:339
Kawana Y, Hirnobu S, Shimada H, Fujita N, Ueda Y, Hayashi A, Araki Y (1987) Epidural ketamine for post-operative pain relief after gynecologic operations: a double-blind study and comparison with epidural morphine. Anesth Analg 66:753
Loomis CW, Aruchachalam KD, Vyas D, Milne B (1992) Potentiation of intrathecal demedetomidine antinociception by i.t. methoxamine in the rat: evidence for an endogenous opioid link. Can J Anaesth 39 [Suppl]: A13
Lund C, Qvitzau S, Greulich A, Hjorsto N-C, Kehlet H (1989) Comparison of the effect of extradural clonidine with those of morphine on postoperative pain, stress responses, cardiopulmonary function and motor and sensory block. Br J Anaesth 63:516
Malinovsky J-M, Cozian A, Lepage J-Y, Mussini J-M, Pinaud M, Souron R (1991) Ketamine and midazolam neurotoxicity in man. Anesthesiology 75:91
Maier C (1993) Calcitonin. In: Zenz M, Jurna I (Hrsg) Lehrbuch der Schmerztherapie. Wissenschaftlicher Verlag, Stuttgart, S 179
Marley WS (1991) AANA journal course: New technologies in anesthesia: Update for nurse anesthesists—Clonidine: An established drug with futuristic indications. AANA Journal Course 59:161.
Melzack R, Wall PD (1965) Pain mechanisms: a new theory. Science 150:971
Mendez R, Eisenach JC, Kashtan K (1990) Epidural clonidine analgesia after cesarean section. Anesthesiology 73:848
Meynadier J, Chrubrasik J, Dubar M, Wünsch E (1985) Intrathecal somatostatin in terminally ill patients: A report of two cases. Pain 23:9
Meynadier J (1986) Administration de substance non-morphinique dans le LCR dans le cadre du traiment des douleurs rebeles en cancérologie. Euromédicine Montpellier. La douleur en cancérlogogie. Editel Paris: 151
Migaly P (1986) The problem of intrathecal ketamine. Br J Anaesth 58:684
Miralles ME, Quirk JG, Clark RB (1986) Subarachnoidal administration of calcitonin produces postoperative analgesia. Anesthesiology 67:590
Mitterschiffthaler G, Huber C, Theiner A, Fuith IC (1987) Selection of patients for intrathecal opioid therapy. ESRA 6th Congress Eur Soc Reg Anaesth, Report 119, MAPAR, Paris
Mollenholt P, Rawal N, Post C, Paulsson I (1987) Neurotoxic and motor actions of somatostatin in the rat after intrathecal administration. ESRA 6th Congress. Eur Soc Reg Anaesth, Report 115, MAPAR, Paris
Mollenholt P, Post C, Rawal N, Freedman J, Hökfelt T, Paulsson I (1988) Antinociceptive and neurotoxic actions of somatostatin in rat spinal cord after intrathecal administration. Pain 32:95
Motsch J, Gräber E, Ludwig K (1990) Addition of clonidine enhances post-operative analgesia from epidural morphine: a double-blind study. Anesthesiology 73:1067
Motsch J (1991) Epidurale und intrathekale Applikation von Alpha-2-Agonisten zur Therapie akuter und tumorassoziierter Schmerzen. Fortschr Anästh 5:89
Müller H, Börner U, Zierski J, Hempelmann G (1987) Intrathecal baclofen for treatment of tetanus-induced spasticity. Anesthesiology 66:76
Nagasaka H, Yaksh TL (1990) Pharmacology of intrathecal adrenergic agonists: cardiovascular and nociceptive reflexes in the halothane-anesthized rats. Anesthesiology 73:1198
Nagawaka I, Omote K, Kitahata LM, Collins JG, Murata K (1990) Serotoninergic mediation of spinal analgesia and its interaction with noradrenergic systems. Anesthesiology 73:474
Naguib M, Yaw A-G, Gamil H, Hesham F, Gyasi HK (1986) Epidural ketamine for postoperative analgesia. Can Anaesth 33:16–21
Naguib M, Sharif AMY, Seeraj M, Gammal ME, Dawlatly AA (1991) Ketamine for caudal analgesia in children: comparison with caudal bupivacaine. Br J Anaesth 67:559
Navarro GH, Gonzalea MJ, Zimman Mansfeld H, Molinaro Apricio T (1986) Epidural administration of calcitonin in pain due to bone metastasis. II Int Symposium: Pain Clinic, Lille (France)
Nishiyama T, Odaka Y, Hirasaki A, Seto K (1991) Epidural midazolam for postoperative pain. Masui 40:1353
Niv D, Witham JG, Loh L (1983) Depression of nociceptive sympathic reflexes by intrathecal administration of midazolam. Br J Anaesth 55:541
Niv D, Davidovich S, Geller E, Urca G (1988) Analgesic and hyperalgesic effects of midazolam: dependence on the route of administration of midazolam. Anesth Analg 67:1169
Ono M, Satoh T (1991) Pharmacological studies on Lappaconitine: antinociception and inhibition of the spinal action of substance P and somatostatin. Jpn J Pharmacol 55:523
Pellerin M, Hardy F, Abergel A, Boule D, Palcci JH (1987) Chronic refractory pain in cancer patient. Usefullness of intrathecal lysine acetylsalicylate in 60 cases. Presse Med 16:1465
Pekoe GM, Smith BA, Smith DJ (1980) Neurochemical basis of ketamine and morphine analgesia. Anesthesiology 53 [Suppl]:S4
Pendeville P, Boven M van, Kock M de (1992) Subarachnoidal clonidine and minimal dose of HB bupivacaine for saddle block. Reg Anesth 17:30
Penn RD, Kroin JS (1985) Continous intrathecal baclofen for severe spacticity. Lancet II:125
Petit J, Ochsenhendler G, Colas G, Leroy A, Winckler C (1989) Comparison of the effect of morphine, clonidine and combination of morphine and clonidine administered epidurally for postoperative analgesia. Anesthesiology [Suppl] 71:647
Polc P, Laurent JP, Scherschlicht R, Haeffley W (1981) Electrophysiological studies on the specific benzodiazepine agonist Ro 15 1788. Nauyn-Schniedberg’s Archiv Pharmacol 316:317
Pomeranz B, Nguyen P (1987) Intrathecal diazepam supresses nociceptive reflexes and potentiates electroacupuncture effects in pentobarbitalanesthetized rats. Neuriosci Lett 77:316
Rattan AK, McDonald JS, Tejwani GA (1991) Differential effects of intrathecal midazolam on morphine-induced antinociception in the rat: role of spinal opioid receptors. Anesth Analg 73:124
Rauck Z (1991) Epidural clonidine for refractory reflex sympathic dystrophy. Anesthesiology [Suppl] 75:A657
Ravat F, Dorne R, Baechle JP, Beaulton A, Ienoir B, Leroy P, Palmier B (1987) Epidural ketamine or morphine for postoperative analgesia. Anesthesiology 66:819
Reddy SVR, Yaksh TL (1980) Spinal noradrenergic terminal system mediates antinociception. Brain Res 189:391
Rigoli M (1983) Epidural analgesia with benzodiazepines. In. Tiengo M, Cousins MJ (eds) Pharmacology of new analgesics and anesthetics. New York, Raven Press, p 69
Rodgers RJ, Randall JI (1987) Benzodiazepine ligands, nociception and defeat analgesia in male mice. Psychopharmacology 91:305
Rosland JH, Hunskaar S, Hole K (1987) The effect of diazepam on nociception in mice. Pharmacol Toxicol 61:111
Rostaing S, Bonner F, Levron JC, Vodinh J, Pluskawa F, Saada M (1991) Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative patients. Anesthesiology 75:420
Sandkühler J, Fu Q-G, Helmchen C (1990) Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurons: comparison with spinal morphine. Neuroscience 34:565
Saissy JM, Vitris M, Demaziere J, Seck M, Marcoux L, Gaye M (1992) Flumazenil counteracts intrathecal baclofen-induced central nervous system depression in tetanus. Anesthesiology 76:1051
Schoeffler R, Taxi J, Auroy P, Woda A, Bazin JE (1991) Subarachnoid midazolam: histologic study in rats and report of its effect on chronic pain in humans. Reg Anesth 16:329
Shaw HL (1982) Subarachnoidal administration of calcitonin: a warning. Lancet II:390
Serrao JM, Stubbs SC, Goodchild CS, Gent JP (1989) Intrathecal midazolam and fentanyl in the rat: evidence for different spinal antinociceptive effects. Anesthesiology 70:780
Serrao JM, Marks RL, Morley SJ, Goodchild CS (1990) Intrathecal midazolam for the treatment of chronic mechanical low back pain: comparison with epidural steroid. Pain 5 [Suppl]:S389
Serrao JM, Goodchild CS, Gent JP (1991) Reversal by naloxone of spinal antinociceptive effects of fentanyl, ketocyclazocine and midazolam. Eur J Anaesth 8:401
Serrao JM, Marks RL, Morley SJ, Goodchild CS (1992) Intrathecal midazolam for the treatment of chronic mechanical low back pain: a controlled comparison with epidural steroid in a pilot study. Pain 48:5
Smith DJ, Westfall DP, Adams PD, Adams JD (1980) Ketamine interacts with opiate receptors as an agonist. Anesthesiology 53 [Suppl]:S5
Smullin DH, Skilling SR, Larson AA (1990) Interactions between substance P, calcitonine gene-related peptide, taurine and excitatory amino acids in the spinal cord. Pain 42:93
Tamsen A, Gordh T (1984) Clonidine is not neurotoxic. Lancet zz:876
Tolksdorf W, Amberger M (1991) Intrathekales Midazolam zur postoperativen Analgesie. Anästhesist 40 [Suppl]:S334
Tryba M, Zenz M (1992) Wirksamkeit und Nebenwirkungen von Opioiden und alpha-2-Adrenzeptoragonisten in der Therapie postoperativer Schmerzen. Der Schmerz 6:182
Van Essen EJ, Bovill JG, Ploeger EJ, Beerman H (1988) Intrathecal morphine and clonidine for control of intractable cancer pain: a case report. Acta Anaesth Belg 39:109
Van Essen EJ, Bovill JG, Ploeger EJ, Houben JJG (1992) Pharmacokinetics of clonidine after epidural administration in surgical patients. Lack of correlation between plasma concentration and analgesia and blood pressure changes. Acta Anaesthesiol Scand 36:300
Vercauteren M, Lauwers E, Meert T, Hert S de, Adraiensen H (1990) Comparison of epidural sufentanil plus clonidine with sufentanil alone for postoperative pain relief. Anaesthesia 45:531
Wang JK (1977) Antinociceptive effect of intrathecally administered serotonin. Anesthesiology 47:269
Wiesenfeld-Hallin Z, Persson A (1984) Subarachnoidal injection of salmon calcitonin does not induce analgesia in rats. Eur J Pharmacol 104:375
Wiesenfeld-Hallin Z (1988) Subarachnoidal lidocaine and calcitonin for postoperative analgesia (letter). Anesth Analg 67:298
Wilson PR, Yaksh TL (1978) Baclofen is antinociceptive in the spinal intrathecal space of animals. Eur J Pharmacol 51:323
Wilcox GL, Carlsson KH, Jochim A, Jurna I (1987) Mutual potentiation of antinociceptive effects of morphine and clonidine on motor and sensory responses in rat spinal cord. Brain Res 405:84
Yaksh TL (1979) Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinociceptive effects of morphine in the periaqueductal gray. Brain Res 106:180
Yaksh TL, Wilson PR (1979) Spinal serotonin terminal system mediates antinociception. J Pharmacol Ther 208:446
Yaksh TL (1989) The role of multiple spinal receptor systems in the modulation of different types of pain. Acta Anaesthesiol Scand 33 [Suppl 91]:35
Yaksh TL, Rudy TA (1982) Central and peripheral mechanisms for the antialgesic action of acetylsalicylic acid. In: Barnett HJM, Hirsh J, Mustard JF (eds) Acetysalicylic acid New aspects for an old drug. Raven Press, New York, p 137
Yanez A, Sabbe MB, Stevens CW, Yaksh TL (1990) Interaction of midazolam and morphine in the spinal cord of the rat. Neuropharmacology 29:359
Zimmermann M (1993) Phsyiologische Grundlagen des Schmerzes und der Schmerztherapie, In: Zenz M, Jurna I (Hrsg) Lehrbuch der Schmerztherapie. Wissenschaftliche Verlagsgesellschaft, Stuttgart, S 179