Changes in Inflammatory Cytokine Levels in Response to Spinal Manipulative Treatment of Low Back Patients: A Single-blind Pilot Clinical Trial.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- Determining proinflammatory cytokine (TNFα and IL-1β) levels in acute and chronic low back pain patients and in healthy asymptomatic subjects.
研究概览
简要总结
It is expected that mechanical low back pain (LBP) is associated with inflammatory changes localized to the affected tissues. Could such changes be detected in cells involved in the inflammatory process in an in vitro model? The investigators wish to test such a model to compare inflammatory markers in acute and chronic LBP patients and also examine the effect of spinal manipulative treatment (SMT) on changing the level of selected key inflammatory markers. The investigators hypothesize that:
- Proinflammatory markers will be elevated while antinflammatory markers will be reduced in acute LBP patients relative to chronic back pain patients as well as in healthy study participants who have no LBP or any inflammatory conditions (controls).
- SMT will cause a reduction in the production of proinflammatory markers while anti-inflammatory markers will increase relative to baseline levels as well as relative to controls
详细描述
Background: Spinal manipulative treatment(SMT) may work by reducing mechanical irritation to joint tissues (1) and thereby diminishing local inflammation. Evidence for an anti-inflammatory effect of instrument-assisted SMT has been observed in an animal model (2). These findings are consistent with the recently proposed hypothesis that the origin of all pain may be associated with inflammation and augmented production of inflammatory mediators (cytokines), principally TNFα (3). TNFα plays a major role in the pathophysiology of neuropathic pain-associated inflammation (4) and has been implicated in spinal pain syndromes, including intervertebral disc-related low back pain (5, 6) and sciatica (7,8). Our recent studies demonstrated that production of inflammatory mediators is elevated in patients with chronic cervical spine pain, both in vitro and in vivo, and accompanied by up-regulation of chemokine (CC) synthesis (9).
Recent reports on clinical (10), animal (2) and human in vitro models (11) suggest that SMT may exert an anti-inflammatory effect. Thus, Song et al. (2) found that SMT reduced inflammatory neuropathic pain. Teodorczyk-Injeyan et al. (11) demonstrated a significant attenuation of pro-inflammatory cytokine production in vitro, and no changes in serum substance P (SP) levels following SMT. Other studies from our laboratory showed that SMT may enhance both the production of and the response to the immunomodulatory cytokine, IL-2, and IL-2-dependent antibody synthesis (12, 13). Reduction in serum TNFα levels has been reported for cervicogenic headache patients (n=2, case studies) (14, 15). These observations suggest that SMT effects may be transduced into cellular components of the immune system.
Thus far, the clinical relevance of the effect of SMT as a modulator of inflammatory mediator production is unknown. Despite evidence of inflammatory pathophysiology of spinal pain (16), including a subtype of non-specific spinal pain (17), only one clinical study (18) evaluated the correlation between serum TNFα levels, pain intensity and back function.
In this proposed study we intend to use a clinical model to investigate the baseline levels of proinflammatory cytokines in acute and chronic low back pain patients and explore the potential anti-inflammatory effect of SMT following a course of manipulative treatments. Thus, Aim 1 is to determine baseline pro-inflammatory cytokine levels in individuals experiencing acute or chronic lower spinal pain of mechanical etiology, and compare them with asymptomatic controls'. Aim 2 is to explore the relationships between SMT, pain level and functional impairment, and the production of inflammatory mediators relative to baseline.
Anti-inflammatory cytokines (IL-10 and IL-1ra) have been found to be produced alongside, and in parallel, with their respective pro-inflammatory counterparts (TNFα and IL-1β), and act in concert to sustain/restore homeostasis (19). The proposed study will include determinations, in addition to pro-inflammatory cytokine (IL-1, TNFα, IL-6) levels, of the levels of IL-1 receptor antagonist (IL-1ra) and IL-10. Assessment of IL-10 synthesis is particularly relevant as this cytokine up-regulates the production of IL-1ra, which competes with active IL-1 for binding to IL-1 receptors, and which acts as a potent natural anti-inflammatory protein (19, 20).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Asymptomatic controls:
- •Adults between the ages of 20 and 60 years
- •No pain of any etiology
- •No inflammatory conditions including musculoskeletal complaints
- •No diabetes
- •No neoplasms
- •No spinal manipulative treatments for the past 4 weeks
- •Willing to sign informed consent
- •For low back patients:
- •Adults between the ages of 20 and 60 years
- •Having low back pain of no longer than 4 weeks (acute) or longer than 12 weeks (chronic), with or without radiation to the lower extremity.
- •No fractures
- •NoInflammatory conditions
- •No other pain complaints
- •No diabetes
- •No spinal manipulative treatments for the past 4 weeks
- •Willing to sign informed consent
排除标准
- •<20 or >60 years of age.
- •Having experienced low back pain longer than 4 wks but less than 12 wks
- •Experiencing less than 3/10 pain as judged by a VAS score determined at time of presentation to study.
- •Failure of clinician to locate a musculoskeletal indicator that will reproduce/localize the patient's pain (e.g., localized muscle tightness, soft tissue tenderness, reproduction of symptoms on digital joint challenge).
- •Currently experiencing significant pain (sprain/strain) anywhere in the body other than the low back.
- •Having been diagnosed with back pain of non-mechanical origin, including seronegative arthropathies, fibromyalgia, inflammatory joint conditions, infections, and tumors.
- •Having been diagnosed with inflammatory conditions in the past (e.g autoimmune diseases, psoriasis), or currently experiencing any inflammatory condition(s) (e.g. allergies, tooth extraction or other dental work).
- •Having been diagnosed with/experienced any infections in past 4 weeks (including common cold, oral/genital herpes, etc).
- •Having a blood clotting disorder.
- •Having received anti-inflammatory, immunosuppressive, immunostimulatory (e.g. immunization) or anticoagulant medications during the past 2 weeks.
- •Having received a spinal manipulative treatment during the past 4 weeks.
- •Unwilling to sign study consent form.
- •Unwilling/unable to adhere to study schedule. -
结局指标
主要结局
Determining proinflammatory cytokine (TNFα and IL-1β) levels in acute and chronic low back pain patients and in healthy asymptomatic subjects.
时间窗: Baseline (time zero) determinations to compare acute vs chronic vs control.
Supernatants from whole blood cultures are collected 24 or 48 hours postincubation, are dispensed in 0.5-1.0 ml aliquots and stored at 76C. Because subject recruitment occurs over a long period,it is not desirable to process samples sporadically. This approach allows using same-batch reagents/bioassay kits for all samples in an effort to decrease error and enhance internal consistency. Results will be expressed as the difference between the values obtained for acute, chronic and control at baseline.
次要结局
- Determining if spinal manipulative treatment will cause significant changes in the level of proinflammatory cytokine production in vitro.(Baseline and 2 weeks i.e on the 7th visit of patients.)
研究者
Stephen Injeyan
Professor and Chair Department of Pathology and Microbiology
Canadian Memorial Chiropractic College