Long-term impact of spinal morphine in the treatment of chronic neuropathic pain on the immune system

• Grant number: 13/15522-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2014
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Manoel Jacobsen Teixeira
• Grantee: Manoel Jacobsen Teixeira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Christiane Pellegrino Rosa

Abstract

The spinal route is considered as an option for further treatment on neuropathic pain refractory to patients who have not achieved adequate pain relief with other treatments, as well as those with sufficient analgesia, but high doses of opioids, either orally or parenteral, or have unacceptable side effects. Increasing evidence suggests that neuropathic pain, chronic use of opioids, conditions that often coexist, leading to activation of microglia cells, resulting in increased synthesis and release of proinflammatory cytokines, and consequent increase in the excitability of neurons in the dorsal horn and central sensitization. The study finds that the neuropathic pain and the prolonged use of intrathecal morphine in patients with chronic neuropathic pain can alter the immune response and correlate with clinical signs of pain worsening, hyperalgesia and tolerance. Poor pain control in patients with chronic neuropathic pain despite treatment with opioids, may correlate directly to changes in inflammatory responses arising from the prolonged use of intrathecal opioidAlthough there is evidence in the literature about the immunomodulatory effects of opioids, few studies have examined the interaction between inflammatory markers and in vivo neuropathic pain in patients with chronic neuropathic pain not due to cancer in the use of intrathecal morphine for a long time. Objectives: Analyze the correlation between chronic neuropathic pain and inflammatory markers in patients in prolonged use of intrathecal morphine and patients with neuropathic pain and are not using opioids. Analyze the possible relationship between the developments of hyperalgesia and / or tolerance and inflammatory markers in patients with chronic neuropathic pain in long-term use of intrathecal morphine.Methodology: Will be evaluated 60 patients, divided into a group with chronic neuropathic pain unrelated to cancer in long term use of intrathecal morphine (n = 20), a group with chronic neuropathic pain unrelated to cancer that do not use opioids by any route of administration (n = 20) and a control group of healthy subjects (n = 20). Will be used in the evaluation sample: Standardized protocol for the clinical, neurological and chronic pain CDHCFMUSP; visual analogue scale measures of pain (VAS), McGill Pain Questionnaire (MPQ), DN4 Questionnaire, measurement of blood cytokines IL1- ², IL-6, IFN-³, IL 17, IL-10, TNF-±, chemokine (MCP-1), leukocyte and lymphocyte count, levels of CD4 and NK cells.Expected ResultsThe identification of inflammatory markers altered in chronic neuropathic pain states and individuals using opioids chronically may be of great assistance to new therapeutic targets, helping the development of more effective treatments in this condition. (AU)