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Neuraxial Opioid-Induced Itch and Its Pharmacological Antagonism

  • Mei-Chuan Ko
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 226)

Abstract

Given its profound analgesic nature, neuraxial opioids are frequently used for pain management. Unfortunately, the high incident rate of itch/pruritus after spinal administration of opioid analgesics reported in postoperative and obstetric patients greatly diminishes patient satisfaction and thus the value of the analgesics. Many endeavors to solve the mystery behind neuraxial opioid-induced itch had not been successful, as the pharmacological antagonism other than the blockade of mu opioid receptors remains elusive. Nevertheless, as the characteristics of all opioid receptor subtypes have become more understood, more studies have shed light on the potential effective treatments. This review discusses the mechanisms underlying neuraxial opioid-induced itch and compares pharmacological evidence in nonhuman primates with clinical findings across diverse drugs. Both nonhuman primate and human studies corroborate that mixed mu/kappa opioid partial agonists seem to be the most effective drugs in ameliorating neuraxial opioid-induced itch while retaining neuraxial opioid-induced analgesia.

Keywords

Agonist Analgesics Antagonist Antipruritics Epidural Intrathecal Itch Monkey Mouse Opioid receptor Pain Pruritus Rat Spinal cord 

Abbreviations

DOP

Delta opioid receptor

GRPR

Gastrin-releasing peptide receptor

KOP

Kappa opioid receptor

MOP

Mu opioid receptor

NOP

Nociceptin/orphanin FQ peptide receptor

Notes

Acknowledgment

Funding from the National Institutes of Health in the United States (DA-013685, AR-059193, and AR-064456) to support the research of neuraxial opioid-induced itch is gratefully acknowledged.

References

  1. Abboud TK, Afrasiabi A, Zhu J, Mantilla M, Reyes A, D’Onofrio L, Khoo N, Mosaad P, Richardson M, Kalra M et al (1989) Epidural morphine or butorphanol augments bupivacaine analgesia during labor. Reg Anesth 14:115–120PubMedGoogle Scholar
  2. Abboud TK, Lee K, Zhu J, Reyes A, Afrasiabi A, Mantilla M, Steffens Z, Chai M (1990) Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. Anesth Analg 71:367–370PubMedGoogle Scholar
  3. Ackerman WE, Juneja MM, Kaczorowski DM, Colclough GW (1989) A comparison of the incidence of pruritus following epidural opioid administration in the parturient. Can J Anaesth 36:388–391PubMedGoogle Scholar
  4. Alhashemi JA, Crosby ET, Grodecki W, Duffy PJ, Hull KA, Gallant C (1997) Treatment of intrathecal morphine-induced pruritus following caesarean section. Can J Anaesth 44:1060–1065PubMedGoogle Scholar
  5. Andrew D, Craig AD (2001) Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 4:72–77PubMedGoogle Scholar
  6. Bailey PL, Rhondeau S, Schafer PG, Lu JK, Timmins BS, Foster W, Pace NL, Stanley TH (1993) Dose–response pharmacology of intrathecal morphine in human volunteers. Anesthesiology 79:49–59, discussion 25APubMedGoogle Scholar
  7. Bailey AG, Valley RD, Freid EB, Calhoun P (1994) Epidural morphine combined with epidural or intravenous butorphanol for postoperative analgesia in pediatric patients. Anesth Analg 79:340–344PubMedGoogle Scholar
  8. Ballantyne JC, Loach AB, Carr DB (1988) Itching after epidural and spinal opiates. Pain 33:149–160PubMedGoogle Scholar
  9. Ben-David B, DeMeo PJ, Lucyk C, Solosko D (2002) Minidose lidocaine-fentanyl spinal anesthesia in ambulatory surgery: prophylactic nalbuphine versus nalbuphine plus droperidol. Anesth Analg 95:1596–1600, table of contentsPubMedGoogle Scholar
  10. Bergasa NV (2008) Pruritus in primary biliary cirrhosis: pathogenesis and therapy. Clin Liver Dis 12:385–406PubMedGoogle Scholar
  11. Bonnet MP, Marret E, Josserand J, Mercier FJ (2008) Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by neuraxial opioids: a quantitative systematic review. Br J Anaesth 101:311–319PubMedGoogle Scholar
  12. Borgeat A, Stirnemann HR (1999) Ondansetron is effective to treat spinal or epidural morphine-induced pruritus. Anesthesiology 90:432–436PubMedGoogle Scholar
  13. Brandt MR, Furness MS, Mello NK, Rice KC, Negus SS (2001) Antinociceptive effects of delta-opioid agonists in Rhesus monkeys: effects on chemically induced thermal hypersensitivity. J Pharmacol Exp Ther 296:939–946PubMedGoogle Scholar
  14. Browning RM, Fellingham WH, O’Loughlin EJ, Brown NA, Paech MJ (2013) Prophylactic ondansetron does not prevent shivering or decrease shivering severity during cesarean delivery under combined spinal epidural anesthesia: a randomized trial. Reg Anesth Pain Med 38:39–43PubMedGoogle Scholar
  15. Butelman ER, Kreek MJ (2013) Kappa opioids: problems and opportunities in analgesia. In: Ko MC, Husbands SM (eds) Research and development of opioid-related ligands. American Chemical Society, Washington DC, pp 245–255Google Scholar
  16. Butelman ER, Negus SS, Ai Y, de Costa BR, Woods JH (1993) Kappa opioid antagonist effects of systemically administered nor-binaltorphimine in a thermal antinociception assay in rhesus monkeys. J Pharmacol Exp Ther 267:1269–1276PubMedGoogle Scholar
  17. Butelman ER, Winger G, Zernig G, Woods JH (1995) Butorphanol: characterization of agonist and antagonist effects in rhesus monkeys. J Pharmacol Exp Ther 272:845–853PubMedGoogle Scholar
  18. Butelman ER, Ko MC, Sobczyk-Kojiro K, Mosberg HI, Van Bemmel B, Zernig G, Woods JH (1998) kappa-Opioid receptor binding populations in rhesus monkey brain: relationship to an assay of thermal antinociception. J Pharmacol Exp Ther 285:595–601PubMedGoogle Scholar
  19. Charuluxananan S, Somboonviboon W, Kyokong O, Nimcharoendee K (2000) Ondansetron for treatment of intrathecal morphine-induced pruritus after cesarean delivery. Reg Anesth Pain Med 25:535–539PubMedGoogle Scholar
  20. Charuluxananan S, Kyokong O, Somboonviboon W, Lertmaharit S, Ngamprasertwong P, Nimcharoendee K (2001) Nalbuphine versus propofol for treatment of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg 93:162–165PubMedGoogle Scholar
  21. Charuluxananan S, Kyokong O, Somboonviboon W, Narasethakamol A, Promlok P (2003) Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg 96:1789–1793, table of contentsPubMedGoogle Scholar
  22. Cohen SE, Ratner EF, Kreitzman TR, Archer JH, Mignano LR (1992) Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. Anesth Analg 75:747–752PubMedGoogle Scholar
  23. Colbert S, O'Hanlon DM, Chambers F, Moriarty DC (1999a) The effect of intravenous tenoxicam on pruritus in patients receiving epidural fentanyl. Anaesthesia 54:76–80PubMedGoogle Scholar
  24. Colbert S, O’Hanlon DM, Galvin S, Chambers F, Moriarty DC (1999b) The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine. Anaesthesia 54:948–952PubMedGoogle Scholar
  25. Cousins MJ, Mather LE (1984) Intrathecal and epidural administration of opioids. Anesthesiology 61:276–310PubMedGoogle Scholar
  26. Cowan A, Gmerek DE (1986) In-vivo studies on kappa opioid receptors. Trends Pharmacol Sci 7:69–72Google Scholar
  27. Davidson S, Zhang X, Yoon CH, Khasabov SG, Simone DA, Giesler GJ Jr (2007) The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons. J Neurosci 27:10007–10014PubMedCentralPubMedGoogle Scholar
  28. Davidson S, Zhang X, Khasabov SG, Simone DA, Giesler GJ Jr (2009) Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons. Nat Neurosci 12:544–546PubMedCentralPubMedGoogle Scholar
  29. Davidson S, Zhang X, Khasabov SG, Moser HR, Honda CN, Simone DA, Giesler GJ Jr (2012) Pruriceptive spinothalamic tract neurons: physiological properties and projection targets in the primate. J Neurophysiol 108:1711–1723PubMedCentralPubMedGoogle Scholar
  30. Dawn AG, Yosipovitch G (2006) Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol 54:527–531PubMedGoogle Scholar
  31. Dershwitz M, Rosow CE, DiBiase PM, Zaslavsky A (1991) Comparison of the sedative effects of butorphanol and midazolam. Anesthesiology 74:717–724PubMedGoogle Scholar
  32. Dominguez JE, Habib AS (2013) Prophylaxis and treatment of the side-effects of neuraxial morphine analgesia following cesarean delivery. Curr Opin Anaesthesiol 26:288–295PubMedGoogle Scholar
  33. Du BX, Song ZM, Wang K, Zhang H, Xu FY, Zou Z, Shi XY (2013) Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials. Can J Anaesth 60:907–917PubMedGoogle Scholar
  34. Dunteman E, Karanikolas M, Filos KS (1996) Transnasal butorphanol for the treatment of opioid-induced pruritus unresponsive to antihistamines. J Pain Symptom Manage 12:255–260PubMedGoogle Scholar
  35. Ellis DJ, Millar WL, Reisner LS (1990) A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after cesarean section. Anesthesiology 72:981–986PubMedGoogle Scholar
  36. Emmerson PJ, Clark MJ, Mansour A, Akil H, Woods JH, Medzihradsky F (1996) Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor. J Pharmacol Exp Ther 278:1121–1127PubMedGoogle Scholar
  37. Gambling DR, Howell P, Huber C, Kozak S (1994) Epidural butorphanol does not reduce side effects from epidural morphine after cesarean birth. Anesth Analg 78:1099–1104PubMedGoogle Scholar
  38. Ganesh A, Maxwell LG (2007) Pathophysiology and management of opioid-induced pruritus. Drugs 67:2323–2333PubMedGoogle Scholar
  39. Gerak LR, France CP (1996) Discriminative stimulus effects of nalbuphine in rhesus monkeys. J Pharmacol Exp Ther 276:523–531PubMedGoogle Scholar
  40. Gerak LR, Butelman ER, Woods JH, France CP (1994) Antinociceptive and respiratory effects of nalbuphine in rhesus monkeys. J Pharmacol Exp Ther 271:993–999PubMedGoogle Scholar
  41. Gmerek DE, Cowan A (1983) An animal model for preclinical screening of systemic antipruritic agents. J Pharmacol Methods 10:107–112PubMedGoogle Scholar
  42. Gmerek DE, Cowan A (1984) In vivo evidence for benzomorphan-selective receptors in rats. J Pharmacol Exp Ther 230:110–115PubMedGoogle Scholar
  43. Gulhas N, Erdil FA, Sagir O, Gedik E, Togal T, Begec Z, Ersoy MO (2007) Lornoxicam and ondansetron for the prevention of intrathecal fentanyl-induced pruritus. J Anesth 21:159–163PubMedGoogle Scholar
  44. Gunter JB, McAuliffe J, Gregg T, Weidner N, Varughese AM, Sweeney DM (2000) Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children. Paediatr Anaesth 10:167–172PubMedGoogle Scholar
  45. Gurkan Y, Toker K (2002) Prophylactic ondansetron reduces the incidence of intrathecal fentanyl-induced pruritus. Anesth Analg 95:1763–1766, table of contentsPubMedGoogle Scholar
  46. Hermens JM, Ebertz JM, Hanifin JM, Hirshman CA (1985) Comparison of histamine release in human skin mast cells induced by morphine, fentanyl, and oxymorphone. Anesthesiology 62:124–129PubMedGoogle Scholar
  47. Horta ML, Morejon LC, da Cruz AW, Dos Santos GR, Welling LC, Terhorst L, Costa RC, Alam RU (2006) Study of the prophylactic effect of droperidol, alizapride, propofol and promethazine on spinal morphine-induced pruritus. Br J Anaesth 96:796–800PubMedGoogle Scholar
  48. Hu E, Calo G, Guerrini R, Ko MC (2010) Long-lasting antinociceptive spinal effects in primates of the novel nociceptin/orphanin FQ receptor agonist UFP-112. Pain 148:107–113PubMedCentralPubMedGoogle Scholar
  49. Iatrou CA, Dragoumanis CK, Vogiatzaki TD, Vretzakis GI, Simopoulos CE, Dimitriou VK (2005) Prophylactic intravenous ondansetron and dolasetron in intrathecal morphine-induced pruritus: a randomized, double-blinded, placebo-controlled study. Anesth Analg 101:1516–1520PubMedGoogle Scholar
  50. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M (2006) The neurobiology of itch. Nat Rev Neurosci 7:535–547PubMedGoogle Scholar
  51. Inan S, Dun NJ, Cowan A (2009) Nalfurafine prevents 5′-guanidinonaltrindole- and compound 48/80-induced spinal c-fos expression and attenuates 5′-guanidinonaltrindole-elicited scratching behavior in mice. Neuroscience 163:23–33PubMedCentralPubMedGoogle Scholar
  52. Jones EA, Bergasa NV (1992) The pruritus of cholestasis and the opioid system. JAMA 268:3359–3362PubMedGoogle Scholar
  53. Jones EA, Molenaar HA, Oosting J (2007) Ondansetron and pruritus in chronic liver disease: a controlled study. Hepatogastroenterology 54:1196–1199PubMedGoogle Scholar
  54. Kendrick WD, Woods AM, Daly MY, Birch RF, DiFazio C (1996) Naloxone versus nalbuphine infusion for prophylaxis of epidural morphine-induced pruritus. Anesth Analg 82:641–647PubMedGoogle Scholar
  55. Kjellberg F, Tramer MR (2001) Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials. Eur J Anaesthesiol 18:346–357PubMedGoogle Scholar
  56. Ko MC (2013) Inhibitory effects of dynorphin-A on spinally administered beta-endorphin- and GRP-induced itch scratching in nonhuman primates. The proceedings of the 7th World Congress on Itch (Boston, MA, USA)Google Scholar
  57. Ko MC, Husbands SM (2009) Effects of atypical kappa-opioid receptor agonists on intrathecal morphine-induced itch and analgesia in primates. J Pharmacol Exp Ther 328:193–200PubMedCentralPubMedGoogle Scholar
  58. Ko MC, Naughton NN (2000) An experimental itch model in monkeys: characterization of intrathecal morphine-induced scratching and antinociception. Anesthesiology 92:795–805PubMedCentralPubMedGoogle Scholar
  59. Ko MC, Naughton NN (2009) Antinociceptive effects of nociceptin/orphanin FQ administered intrathecally in monkeys. J Pain 10:509–516PubMedCentralPubMedGoogle Scholar
  60. Ko MC, Lee H, Harrison C, Clark MJ, Song HF, Naughton NN, Woods JH, Traynor JR (2003a) Studies of micro-, kappa-, and delta-opioid receptor density and G protein activation in the cortex and thalamus of monkeys. J Pharmacol Exp Ther 306:179–186PubMedGoogle Scholar
  61. Ko MC, Lee H, Song MS, Sobczyk-Kojiro K, Mosberg HI, Kishioka S, Woods JH, Naughton NN (2003b) Activation of kappa-opioid receptors inhibits pruritus evoked by subcutaneous or intrathecal administration of morphine in monkeys. J Pharmacol Exp Ther 305:173–179PubMedGoogle Scholar
  62. Ko MC, Song MS, Edwards T, Lee H, Naughton NN (2004) The role of central mu opioid receptors in opioid-induced itch in primates. J Pharmacol Exp Ther 310:169–176PubMedGoogle Scholar
  63. Ko MC, Wei H, Woods JH, Kennedy RT (2006) Effects of intrathecally administered nociceptin/orphanin FQ in monkeys: behavioral and mass spectrometric studies. J Pharmacol Exp Ther 318:1257–1264PubMedGoogle Scholar
  64. Ko MC, Woods JH, Fantegrossi WE, Galuska CM, Wichmann J, Prinssen EP (2009) Behavioral effects of a synthetic agonist selective for nociceptin/orphanin FQ peptide receptors in monkeys. Neuropsychopharmacology 34:2088–2096PubMedCentralPubMedGoogle Scholar
  65. Korhonen AM, Valanne JV, Jokela RM, Ravaska P, Korttila K (2003) Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl. Acta Anaesthesiol Scand 47:1292–1297PubMedGoogle Scholar
  66. Krajnik M, Zylicz Z (2001) Understanding pruritus in systemic disease. J Pain Symptom Manage 21:151–168PubMedGoogle Scholar
  67. Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H (2010) Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 25:1251–1257PubMedGoogle Scholar
  68. Kumagai H, Ebata T, Takamori K, Miyasato K, Muramatsu T, Nakamoto H, Kurihara M, Yanagita T, Suzuki H (2012) Efficacy and safety of a novel k-agonist for managing intractable pruritus in dialysis patients. Am J Nephrol 36:175–183PubMedGoogle Scholar
  69. Kumar K, Singh SI (2013) Neuraxial opioid-induced pruritus: an update. J Anaesthesiol Clin Pharmacol 29:303–307PubMedCentralPubMedGoogle Scholar
  70. Kumor KM, Haertzen CA, Johnson RE, Kocher T, Jasinski D (1986) Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo. J Pharmacol Exp Ther 238:960–968PubMedGoogle Scholar
  71. Kuraishi Y, Yamaguchi T, Miyamoto T (2000) Itch-scratch responses induced by opioids through central mu opioid receptors in mice. J Biomed Sci 7:248–252PubMedGoogle Scholar
  72. Laporte AM, Doyen C, Nevo IT, Chauveau J, Hauw JJ, Hamon M (1996) Autoradiographic mapping of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors in the aged human spinal cord. J Chem Neuroanat 11:67–75PubMedGoogle Scholar
  73. Lawhorn CD, Brown RE Jr (1994) Epidural morphine with butorphanol in pediatric patients. J Clin Anesth 6:91–94PubMedGoogle Scholar
  74. Lawhorn CD, McNitt JD, Fibuch EE, Joyce JT, Leadley RJ Jr (1991) Epidural morphine with butorphanol for postoperative analgesia after cesarean delivery. Anesth Analg 72:53–57PubMedGoogle Scholar
  75. Lawhorn CD, Boop FA, Brown RE Jr, Andelman PD, Schmitz ML, Kymer PJ, Shirey R (1995) Continuous epidural morphine/butorphanol infusion following selective dorsal rhizotomy in children. Childs Nerv Syst 11:621–624PubMedGoogle Scholar
  76. Lee H, Naughton NN, Woods JH, Ko MC (2003) Characterization of scratching responses in rats following centrally administered morphine or bombesin. Behav Pharmacol 14:501–508PubMedCentralPubMedGoogle Scholar
  77. Lee LH, Irwin MG, Lim J, Wong CK (2004) The effect of celecoxib on intrathecal morphine-induced pruritus in patients undergoing caesarean section. Anaesthesia 59:876–880PubMedGoogle Scholar
  78. Lee H, Naughton NN, Woods JH, Ko MC (2007) Effects of butorphanol on morphine-induced itch and analgesia in primates. Anesthesiology 107:478–485PubMedCentralPubMedGoogle Scholar
  79. Liao CC, Chang CS, Tseng CH, Sheen MJ, Tsai SC, Chang YL, Wong SY (2011) Efficacy of intramuscular nalbuphine versus diphenhydramine for the prevention of epidural morphine-induced pruritus after cesarean delivery. Chang Gung Med J 34:172–178PubMedGoogle Scholar
  80. Lim GJ, Ishiuji Y, Dawn A, Harrison B, Kim do W, Atala A, Yosipovitch G (2008) In vitro and in vivo characterization of a novel liposomal butorphanol formulation for treatment of pruritus. Acta Derm Venereol 88:327–330PubMedGoogle Scholar
  81. Lin AP, Ko MC (2013) The therapeutic potential of nociceptin/orphanin FQ receptor agonists as analgesics without abuse liability. ACS Chem Neurosci 4:214–224PubMedCentralPubMedGoogle Scholar
  82. Liu XY, Liu ZC, Sun YG, Ross M, Kim S, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH, Chen ZF (2011) Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 147:447–458PubMedCentralPubMedGoogle Scholar
  83. McMahon SB, Koltzenburg M (1992) Itching for an explanation. Trends Neurosci 15:497–501PubMedGoogle Scholar
  84. Molinari S, Camarda V, Rizzi A, Marzola G, Salvadori S, Marzola E, Molinari P, McDonald J, Ko MC, Lambert DG, Calo G, Guerrini R (2013) [Dmt1]N/OFQ(1–13)-NH2: a potent nociceptin/orphanin FQ and opioid receptor universal agonist. Br J Pharmacol 168:151–162PubMedCentralPubMedGoogle Scholar
  85. Morgan PJ, Mehta S, Kapala DM (1991) Nalbuphine pretreatment in cesarean section patients receiving epidural morphine. Reg Anesth 16:84–88PubMedGoogle Scholar
  86. Moser HR, Giesler GJ Jr (2013) Itch and analgesia resulting from intrathecal application of morphine: contrasting effects on different populations of trigeminothalamic tract neurons. J Neurosci 33:6093–6101PubMedCentralPubMedGoogle Scholar
  87. Oldfield S, Braksator E, Rodriguez-Martin I, Bailey CP, Donaldson LF, Henderson G, Kelly E (2008) C-terminal splice variants of the mu-opioid receptor: existence, distribution and functional characteristics. J Neurochem 104:937–945PubMedGoogle Scholar
  88. Palmer CM, Emerson S, Volgoropolous D, Alves D (1999) Dose–response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology 90:437–444PubMedGoogle Scholar
  89. Penning JP, Samson B, Baxter AD (1988) Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine. Can J Anaesth 35:599–604PubMedGoogle Scholar
  90. Peters GR, Ward NJ, Antal EG, Lai PY, deMaar EW (1987) Diuretic actions in man of a selective kappa opioid agonist: U-62,066E. J Pharmacol Exp Ther 240:128–131PubMedGoogle Scholar
  91. Pirat A, Tuncay SF, Torgay A, Candan S, Arslan G (2005) Ondansetron, orally disintegrating tablets versus intravenous injection for prevention of intrathecal morphine-induced nausea, vomiting, and pruritus in young males. Anesth Analg 101:1330–1336PubMedGoogle Scholar
  92. Preston KL, Jasinski DR (1991) Abuse liability studies of opioid agonist-antagonists in humans. Drug Alcohol Depend 28:49–82PubMedGoogle Scholar
  93. Rawal N, Schott U, Dahlstrom B, Inturrisi CE, Tandon B, Sjostrand U, Wennhager M (1986) Influence of naloxone infusion on analgesia and respiratory depression following epidural morphine. Anesthesiology 64:194–201PubMedGoogle Scholar
  94. Remmers AE, Clark MJ, Mansour A, Akil H, Woods JH, Medzihradsky F (1999) Opioid efficacy in a C6 glioma cell line stably expressing the human kappa opioid receptor. J Pharmacol Exp Ther 288:827–833PubMedGoogle Scholar
  95. Rosow CE, Moss J, Philbin DM, Savarese JJ (1982) Histamine release during morphine and fentanyl anesthesia. Anesthesiology 56:93–96PubMedGoogle Scholar
  96. Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, Hu L, Mok SI, Shah A, Savner EM, Tolias C, Corfas R, Chen S, Inquimbert P, Xu Y, McInnes RR, Rice FL, Corfas G, Ma Q, Woolf CJ, Greenberg ME (2010) Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 65:886–898PubMedCentralPubMedGoogle Scholar
  97. Sakai T, Fukano T, Sumikawa K (2001) IV butorphanol reduces analgesia but not pruritus or nausea associated with intrathecal morphine. Can J Anaesth 48:831–832PubMedGoogle Scholar
  98. Sarvela PJ, Halonen PM, Soikkeli AI, Kainu JP, Korttila KT (2006) Ondansetron and tropisetron do not prevent intraspinal morphine- and fentanyl-induced pruritus in elective cesarean delivery. Acta Anaesthesiol Scand 50:239–244PubMedGoogle Scholar
  99. Schröder W, Lambert DG, Ko MC, Koch T (2014) Functional plasticity of the N/OFQ-NOP receptor system determines analgesic properties of NOP receptor agonists. Br J Pharmacol 171:3777–3800. doi: 10.1111/bph.12744 PubMedGoogle Scholar
  100. Simone DA, Zhang X, Li J, Zhang JM, Honda CN, LaMotte RH, Giesler GJ Jr (2004) Comparison of responses of primate spinothalamic tract neurons to pruritic and algogenic stimuli. J Neurophysiol 91:213–222PubMedGoogle Scholar
  101. Somrat C, Oranuch K, Ketchada U, Siriprapa S, Thipawan R (1999) Optimal dose of nalbuphine for treatment of intrathecal-morphine induced pruritus after caesarean section. J Obstet Gynaecol Res 25:209–213PubMedGoogle Scholar
  102. Sukhtankar DD, Ko MC (2013) Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice. PLoS One 8:e67422PubMedCentralPubMedGoogle Scholar
  103. Sukhtankar DD, Lee H, Rice KC, Ko MC (2014) Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain. Psychopharmacology 231:1377–1387PubMedCentralPubMedGoogle Scholar
  104. Szarvas S, Harmon D, Murphy D (2003) Neuraxial opioid-induced pruritus: a review. J Clin Anesth 15:234–239PubMedGoogle Scholar
  105. Tamdee D, Charuluxananan S, Punjasawadwong Y, Tawichasri C, Patumanond J, Sriprajittichai P (2009) A randomized controlled trial of pentazocine versus ondansetron for the treatment of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Anesth Analg 109:1606–1611PubMedGoogle Scholar
  106. Thomas DA, Williams GM, Iwata K, Kenshalo DR Jr, Dubner R (1992) Effects of central administration of opioids on facial scratching in monkeys. Brain Res 585:315–317PubMedGoogle Scholar
  107. To TH, Clark K, Lam L, Shelby-James T, Currow DC (2012) The role of ondansetron in the management of cholestatic or uremic pruritus–a systematic review. J Pain Symptom Manage 44:725–730PubMedGoogle Scholar
  108. Togashi Y, Umeuchi H, Okano K, Ando N, Yoshizawa Y, Honda T, Kawamura K, Endoh T, Utsumi J, Kamei J, Tanaka T, Nagase H (2002) Antipruritic activity of the kappa-opioid receptor agonist, TRK-820. Eur J Pharmacol 435:259–264PubMedGoogle Scholar
  109. Tzeng JI, Chu KS, Ho ST, Cheng KI, Liu KS, Wang JJ (2003) Prophylactic iv ondansetron reduces nausea, vomiting and pruritus following epidural morphine for postoperative pain control. Can J Anaesth 50:1023–1026PubMedGoogle Scholar
  110. Vivian JA, DeYoung MB, Sumpter TL, Traynor JR, Lewis JW, Woods JH (1999) kappa-Opioid receptor effects of butorphanol in rhesus monkeys. J Pharmacol Exp Ther 290:259–265PubMedGoogle Scholar
  111. Waeber C, Dixon K, Hoyer D, Palacios JM (1988) Localisation by autoradiography of neuronal 5-HT3 receptors in the mouse CNS. Eur J Pharmacol 151:351–352PubMedGoogle Scholar
  112. Walsh SL, Strain EC, Abreu ME, Bigelow GE (2001) Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans. Psychopharmacology (Berl) 157:151–162Google Scholar
  113. Wang JK, Nauss LA, Thomas JE (1979) Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149–151PubMedGoogle Scholar
  114. Wang JJ, Ho ST, Tzeng JI (1998) Comparison of intravenous nalbuphine infusion versus naloxone in the prevention of epidural morphine-related side effects. Reg Anesth Pain Med 23:479–484PubMedGoogle Scholar
  115. Wang Y, Tang K, Inan S, Siebert D, Holzgrabe U, Lee DY, Huang P, Li JG, Cowan A, Liu-Chen LY (2005) Comparison of pharmacological activities of three distinct kappa ligands (Salvinorin A, TRK-820 and 3FLB) on kappa opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo. J Pharmacol Exp Ther 312:220–230PubMedGoogle Scholar
  116. Waxler B, Mondragon SA, Patel SN, Nedumgottil K (2004) Prophylactic ondansetron does not reduce the incidence of itching induced by intrathecal sufentanil. Can J Anaesth 51:685–689PubMedGoogle Scholar
  117. Waxler B, Dadabhoy ZP, Stojiljkovic L, Rabito SF (2005) Primer of postoperative pruritus for anesthesiologists. Anesthesiology 103:168–178PubMedGoogle Scholar
  118. Weiskopf RB, Reid IA, Fisher DM, Holmes MA, Rosen JI, Keil LC (1987) Effects of fentanyl on vasopressin secretion in human subjects. J Pharmacol Exp Ther 242:970–973PubMedGoogle Scholar
  119. Wells J, Paech MJ, Evans SF (2004) Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron. Int J Obstet Anesth 13:35–39PubMedGoogle Scholar
  120. Wittels B, Glosten B, Faure EA, Moawad AH, Ismail M, Hibbard J, Amundsen L, Binstock W, Senal JA, Cox SM et al (1993) Opioid antagonist adjuncts to epidural morphine for postcesarean analgesia: maternal outcomes. Anesth Analg 77:925–932PubMedGoogle Scholar
  121. Wu Z, Kong M, Wang N, Finlayson RJ, De Tran QH (2012) Intravenous butorphanol administration reduces intrathecal morphine-induced pruritus after cesarean delivery: a randomized, double-blind, placebo-controlled study. J Anesth 26:752–757PubMedGoogle Scholar
  122. Yaksh TL, Rudy TA (1976) Analgesia mediated by a direct spinal action of narcotics. Science 192:1357–1358PubMedGoogle Scholar
  123. Yazigi A, Chalhoub V, Madi-Jebara S, Haddad F, Hayek G (2002) Prophylactic ondansetron is effective in the treatment of nausea and vomiting but not on pruritus after cesarean delivery with intrathecal sufentanil-morphine. J Clin Anesth 14:183–186PubMedGoogle Scholar
  124. Yeh HM, Chen LK, Lin CJ, Chan WH, Chen YP, Lin CS, Sun WZ, Wang MJ, Tsai SK (2000) Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Anesth Analg 91:172–175PubMedGoogle Scholar
  125. Zhu J, Luo LY, Li JG, Chen C, Liu-Chen LY (1997) Activation of the cloned human kappa opioid receptor by agonists enhances [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of ligands. J Pharmacol Exp Ther 282:676–684PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Physiology and PharmacologyWake Forest University School of MedicineWinston-SalemUSA

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