| Background. Nearly one-half of cancer survivors suffer from chronic pain, of which over 30% is classified as neuropathic, a consequence of nerve injury. Acute pain has been shown to activate the stress response and enhance postoperative metastatic susceptibility. Few studies have reported on the effects of chronic neuropathic pain (CNP) on immunity, and none have examined the impact of CNP on immune defenses against tumor development.; Purpose. Using an established model of CNP, spinal nerve ligation (SNL), in male Fischer 344 rats, characterize the effects of SNL on the following outcomes over the first six weeks postoperative: (a) CNP behaviors: mechanical allodynia, evidenced by decreased paw withdrawal threshold to tactile stimuli; (b) immune function: (1) levels of spinal cord cytokines gamma interferon (IFN-γ) and interleukin-4 (IL-4), which respectively reflect the balance between cellular and antibody-mediated immune activity; (2) lung clearance of syngeneic natural killer cell (NK)-sensitive mammary adenocarcinoma (MADB106) cells; (c) neuroendocrine activation: plasma corticosterone levels.; Design and methods. A 2 x 7 factorial design was employed for immune and neuroendocrine outcomes: SNL vs. sham surgery; by seven time points during the first six weeks postoperative; plus an untreated control group. Both cross-sectional and repeated measures designs were used for behavioral testing at five postoperative time points. Sixteen hours before blood and organ harvesting, radioisotope-labeled MADB106 cells were injected intravenously. These tumor cells metastasize only to the lungs; tumor clearance was assessed by measuring lung radioactivity. Cytokine and corticosterone levels were assayed using commercial kits.; Findings and implications. Although CNP behaviors were consistently evident in animals that underwent SNL, there were no significant changes in corticosterone or NK-mediated destruction of tumor cells. In the spinal cord, IL-4 was significantly increased and IFN-γ/IL-4 ratio significantly decreased in SNL animals, indicating a shift toward antibody-mediated immune function over cellular immunity. Although the direct health consequences of these alterations are not clear, both human and animal studies associated tumor progression and refractoriness to treatment with similar cytokine alterations. Findings from this study may provide insights into the potential impact of CNP on immune defenses against cancer and pave the way for intervention studies. |
