Transcutaneous electrical nerve stimulation attenuates postsurgical allodynia and suppresses spinal substance P and proinflammatory cytokine release in rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. OBJECTIVE: The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). DESIGN: This was an experimental study. METHODS: High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and 10g) were evaluated. RESULTS: The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR-operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1ß) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1ß. LIMITATIONS: The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. CONCLUSIONS: The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR-operated rats.

Forced treadmill running suppresses postincisional pain and inhibits upregulation of substance P and cytokines in rat dorsal root ganglion.

UNLABELLED: Exercise causes a variety of psychophysical effects (eg, alterations in pain sensation). Tissue injury induces mediator releases in the spinal cord resulting in pain hypersensitivity; however, the contribution of the dorsal root ganglion (DRG) is poorly understood. In this study, we tested if forced treadmill running can attenuate postoperative pain and alter substance P (SP) or proinflammatory cytokine level in the DRG by using a rat model of skin/muscle incision and retraction (SMIR). We evaluated mechanical sensitivity to von Frey stimuli (6 and 15 g) and expression of SP, interleukin-1ß, and interleukin-6 in the DRG of sham-operated sedentary rats, SMIR sedentary rats, sham-operated rats with forced treadmill running, and SMIR rats with forced treadmill running. At postoperative day 8, trained rats ran for 5 days per week for 4 weeks on a treadmill 70 minutes/d with an intensity of 18 m/min. On postoperative day 6, SMIR sedentary rats displayed a significant mechanical hypersensitivity that persisted until postoperative day 35. By comparison, SMIR-operated rats, which received forced treadmill running, exhibited a quick recovery from mechanical hypersensitivity. SMIR sedentary rats showed an upregulation of SP, interleukin-1ß, and interleukin-6 in the DRG at postoperative days 14 and 28, whereas SMIR-operated rats receiving forced treadmill running reversed this upregulation at postoperative day 28. We concluded that forced treadmill running alleviated persistent postincisional pain caused by SMIR surgery. This appears to be protective against postoperative pain, which probably relates to the downturn in excess SP, interleukin-1ß, and interleukin-6 in the DRG. PERSPECTIVE: Controlling the expression of SP, interleukin-6, and interleukin-1ß in the DRG can help manage postoperative pain. This finding could potentially help clinicians and physical therapists who seek to examine how exercise may attenuate postsurgical pain and its mechanism.

High-frequency transcutaneous electrical nerve stimulation attenuates postsurgical pain and inhibits excess substance P in rat dorsal root ganglion.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a common therapeutic modality for pain management, but its effectiveness in skin/muscle incision and retraction (SMIR)-evoked pain is unknown. We aimed to examine the effects of TENS on postoperative pain and the levels of substance P (SP), N-methyl-D-aspartate receptor 1 (NR1), and interleukin 1ß (IL-1ß) in rat dorsal root ganglion (DRG). METHODS: High-frequency (100 Hz) TENS was administered daily beginning on postoperative day 1 (POD1) and continued until animal subjects were killed for tissues. Mechanical sensitivity to von Frey stimuli (6g and 15g) and the levels of NR1, SP, and IL-1ß in DRG were assessed in the sham-operated, SMIR-operated, TENS after SMIR surgery, and placebo-TENS after SMIR surgery groups. RESULTS: Skin/muscle incision and retraction rats exhibited a significant hypersensitivity to von Frey stimuli on POD3. In contrast with SMIR rats, SMIR-operated rats receiving TENS therapy demonstrated a rapid recovery of mechanical hypersensitivity. The SMIR-operated rats showed an up-regulation of NR1, SP, and IL-1ß in DRG on PODs 14 and 28, whereas the SMIR-operated rats after TENS administration reversed this up-regulation. By contrast, the placebo-TENS after SMIR operation did not alter postsurgical pain nor the levels of NR1, SP, and IL-1ß. CONCLUSIONS: Our data demonstrated that TENS intervention reduced persistent postoperative pain caused by SMIR operation. Up-regulation of NR1, SP, and IL-1ß in DRG, activated after SMIR surgery, is important in the development of prolonged postincisional pain. The TENS pain relief may be related to the suppression of NR1, SP, and IL-1ß in DRG of SMIR rats.

Exercise training attenuates postoperative pain and expression of cytokines and N-methyl-D-aspartate receptor subunit 1 in rats.

BACKGROUND: Exercise creates a variety of psychophysical effects, including altered pain perception. We investigated whether physical exercise reduces postincisional pain and cytokine and N-methyl-D-aspartate receptor 1 (NR1) expression in a rat model of skin/muscle incision and retraction (SMIR)-evoked pain. METHODS: Male Sprague-Dawley rats were divided randomly into 4 groups: sham operated, SMIR-sedentary (SS), SMIR-exercise, and sham operated-exercise. On postoperative day 8, trained rats started to run on a treadmill 55 min/d with an intensity of 18 meter/minute (m/min), 5 days per week for 4 weeks. NR1, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) expressions in the spinal cord as well as mechanical hypersensitivity following SMIR surgery were assessed for 6 to 35 days. RESULTS: On postoperative day 6, SMIR-sedentary rats exhibited a marked hypersensitivity to von Frey stimuli. By contrast, SMIR-operated rats undergoing exercise demonstrated a quick recovery of mechanical hypersensitivity. The levels of TNF-α, IL-6, and NR1 in the spinal cord were significantly increased in SS rats when compared with sham-operated rats on postoperative days 6, 21, and 35 after SMIR surgery. After the 4-week exercise intervention, the SMIR-exercise group showed lower NR1, TNF-α, and IL-6 expression in the spinal cord than those in the SS group. CONCLUSIONS: These results suggest that exercise training decreases persistent postsurgical pain caused by SMIR surgery. There appears to be a protective effect, probably relating to the decrease of NR1, TNF-α, and IL-6 expression in the spinal cord of SMIR rats, after exercise intervention.