DOI: 10.1097/01.aoa.0000344692.06228.62

,  

Issn Print: 0275-665X

Publication Date: 2009/03/01


Print

Local and Systemic Release of Cytokines, Nerve Growth Factor, Prostaglandin E2, and Substance P in Incisional Wounds and Serum After Cesarean Delivery

B. Carvalho; D.J. Clark; M.S. Angst

    loading  Checking for direct PDF access through Ovid

Excerpt

Growing evidence indicates that non-neuronal cells (immune cells, keratinocytes, and fibroblasts), through biochemical mediators, affect pain processing by the nervous system in inflamed tissue and influence pain maintenance in damaged peripheral nerves and spinal neural elements. After tissue injury, resident and migrating cells release cytokines and chemokines that help initiate and maintain pain and hyperalgesia. A number of animal studies have indicated that proinflammatory and anti-inflammatory cytokines, prostanoids, neuropeptides, and neurotrophins are important in processing acute pain and chronic pain stress; however, human studies are sparse, partly because of the difficulty in measuring them at the site of injury. The authors of this prospective study tested the feasibility of a method of direct sampling of surgical wound exudate to allow serial measurement of proinflammatory and anti-inflammatory cytokines, nerve growth factor (NGF), prostaglandin-E2 (PG-E2), and substance P (SP) in “real-time,” after cesarean delivery (CS). They also aimed to determine correlations between concentrations of various individual mediators in the wound exudates, patient serum, maternal analgesic consumption, and measurements of postoperative pain.
Twenty healthy parturients with term, singleton pregnancies having elective CS under spinal anesthesia were enrolled. Before anesthesia, all women received lactated Ringer solution, hetastarch, metoclopramide, and ranitidine IV. Anesthesia consisted of intrathecal hyperbaric bupivacaine (12 mg), fentanyl (10 μg), and morphine (0.2 mg). Thirty minutes after surgery, all patients received oral ibuprofen every 6 hours until 48 hours. Breakthrough pain was managed with an oral opioid (oxycodone/acetaminophen), 1 to 2 tablets every 4 hours as needed. Wound exudate (1 mL) was collected at 1, 6, and 24 hours after CS via a 3-way stopcock system that also continuously delivered normal saline subcutaneously into the wound (2 mL/h) to avoid catheter blockage. In the first 10 women, exudate was also collected at 48 hours and 10 mL of blood was collected at baseline, and at 6, 24, and 48 hours post-CS. Exudate and serum mediators, pain scores (10-point visual analog scale), and analgesic consumption were measured at 1, 6, 4, and 48 hours.
All 20 women had uncomplicated surgeries and completed the study. In the exudate, 19 of 20 mediators were reliably detected, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, and IL-17; tumor necrosis factor-α; interferon-γ; granulocyte colony stimulating factor; granulocyte-macrophage colony stimulating factor; monocyte chemoattractant protein-1 and macrophage inflammatory protein-1β; NGF; PG-E2; and SP. Wound PG-E2 and various cytokines peaked early, whereas NGF had a delayed release. No correlations were found between the concentration versus time profile of wound and serum cytokines. Analgesic consumption after CS was negatively correlated with IL-1β, IL-6, and granulocyte colony stimulating factor concentrations found in wound exudate.
The authors concluded that this method of measuring nociceptive and inflammatory mediators in surgical wounds in real-time is feasible, providing an excellent pain model for studying the role of these mediators in postoperative pain. The negative correlation between analgesic consumption and certain mediators requires further investigation.

Related Topics

    loading  Loading Related Articles