Intrathecal Morphine Suppresses Immune Function in Rats with Inflammatory-induced Pain

Acute and chronic systemic administration of morphine is known to suppress immune function; however, the effect of chronic intrathecal (IT) morphine on immune function in inflammatory-induced pain is still unclear. This study examined the effects on the immune system of IT morphine in rats with formalin-induced pain. Lumbar IT catheters were implanted in rats and saline or 2.5, 5.0 or 10.0 μg/h morphine were administered for 7 days. On the last day, formalin-induced inflammatory pain was induced in rat hind paws and pain intensity was assessed. Rat spleens were then harvested for immune function assay. The IT morphine induced a dose-dependent analgesic effect and lactic acid dehydrogenase release assay showed dose-dependent suppression of natural killer cell activity. Concanavalin-A-induced splenocyte proliferation assay showed IT morphine to suppress T lymphocyte function in a dose-dependent manner. Flow cytometry showed IT morphine significantly to decrease T lymphocyte function and the percentages of T lymphocyte subsets in a dose-dependent manner. Hence, in inflammatory-induced pain IT morphine was found to suppress immune function. Chronic IT morphine should be used cautiously to treat chronic pain in immunocompromised cases.

[1]  N. Callizot,et al.  Antinociceptive efficacy of lacosamide in rat models for tumor- and chemotherapy-induced cancer pain. , 2007, European journal of pharmacology.

[2]  P. Sacerdote,et al.  Opioids and immune system , 2006, Palliative medicine.

[3]  I. Chaudry,et al.  Opiate analgesics contribute to the development of post-injury immunosuppression. , 2005, The Journal of surgical research.

[4]  S. McMahon,et al.  Role of the Immune system in chronic pain , 2005, Nature Reviews Neuroscience.

[5]  D. Lysle,et al.  Morphine-induced alterations of immune status are blocked by the dopamine D2-like receptor agonist 7-OH-DPAT , 2004, Journal of Neuroimmunology.

[6]  Richard Taylor,et al.  Intrathecal Morphine for Postoperative Analgesia: A Randomized, Controlled, Dose-Ranging Study After Hip and Knee Arthroplasty , 2003, Anesthesia and analgesia.

[7]  N. C. Alonzo,et al.  Opioids, immunology, and host defenses of intravenous drug abusers. , 2002, Infectious disease clinics of North America.

[8]  H. Loh,et al.  Morphine modulates lymph node‐derived T lymphocyte function: role of caspase‐3, ‐8, and nitric oxide , 2001, Journal of leukocyte biology.

[9]  Mao-tsun Lin,et al.  Effects of morphine on immune response in rats with sciatic constriction injury , 2000, Pain.

[10]  Y. Nomoto,et al.  Intrathecal morphine suppresses NK cell activity following abdominal surgery , 2000, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[11]  T. Eisenstein,et al.  Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations , 1998, Journal of Neuroimmunology.

[12]  T. Yaksh,et al.  Equianalgesic Doses of Subcutaneous but Not Intrathecal Morphine Alter Phenotypic Expression of Cell Surface Markers and Mitogen‐induced Proliferation in Rat Lymphocytes , 1996, Anesthesiology.

[13]  F. Stüber,et al.  Phytohemagglutinin-dependent T-cell proliferation is not impaired by morphine. , 1996, Methods and findings in experimental and clinical pharmacology.

[14]  D. Lysle,et al.  Assessment of the involvement of central nervous system and peripheral opioid receptors in the immunomodulatory effects of acute morphine treatment in rats. , 1996, The Journal of pharmacology and experimental therapeutics.

[15]  A. Howell,et al.  Morphine Inhibits Spontaneous and Cytokine-enhanced Natural Killer Cell Cytotoxicity in Volunteers , 1995, Anesthesiology.

[16]  B. Fuchs,et al.  A mechanism of action for morphine-induced immunosuppression: corticosterone mediates morphine-induced suppression of natural killer cell activity. , 1994, The Journal of pharmacology and experimental therapeutics.

[17]  B. Bayer,et al.  Acute immunosuppressive effects of morphine: lack of involvement of pituitary and adrenal factors. , 1994, The Journal of pharmacology and experimental therapeutics.

[18]  D. Lysle,et al.  Alterations of Immune Status Induced by the Sympathetic Nervous System: Immunomodulatory Effects of DMPP Alone and in Combination with Morphine , 1993, Brain, Behavior, and Immunity.

[19]  M. Tuominen,et al.  Comparison of intrathecal fentanyl infusion with intrathecal morphine infusion or bolus for postoperative pain relief after hip arthroplasty. , 1993, Anesthesia and analgesia.

[20]  B. Fuchs,et al.  Morphine-induced alterations in thymocyte subpopulations of B6C3F1 mice. , 1993, The Journal of pharmacology and experimental therapeutics.

[21]  B. Bayer,et al.  Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism , 1990, Neuropharmacology.

[22]  P. Skolnick,et al.  Morphine-induced immune alterations in vivo. , 1990, Cellular immunology.

[23]  T. Whiteside,et al.  T-lymphocyte subsets in gut and blood of liver transplant recipients with and without cytomegalovirus gastroenteritis , 1989, Digestive Diseases and Sciences.

[24]  T. Whiteside,et al.  The role of natural killer cells in human disease. , 1989, Clinical immunology and immunopathology.

[25]  A. Pert,et al.  The periaqueductal gray matter mediates opiate-induced immunosuppression. , 1989, Science.

[26]  JamesW. Lewis,et al.  Effects of footshock stress and morphine on natural killer lymphocytes in rats: studies of tolerance and cross-tolerance , 1986, Brain Research.

[27]  C. Korzeniewski,et al.  An enzyme-release assay for natural cytotoxicity. , 1983, Journal of immunological methods.

[28]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[29]  D. Dubuisson,et al.  The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats , 1977, Pain.

[30]  T. Yaksh,et al.  Chronic catheterization of the spinal subarachnoid space , 1976, Physiology & Behavior.

[31]  R. Garret,et al.  Susceptibility of addicts to infection and neoplasia. , 1972, The New England journal of medicine.

[32]  K. Edwards.  More disadvantages of bottle feeding. , 1972, The New England journal of medicine.

[33]  H. Beckett.  Systemic infections in heroin addicts. , 1968, Lancet.

[34]  C. Frey,et al.  Intrathecal morphine delivered via subcutaneous pump for intractable pain in pancreatic cancer. , 1999, Surgical neurology.