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Spinal Manipulative Therapy Reduces Inflammatory Cytokines but Not Substance P Production in Normal Subjects
Abstract
To examine the effect of a single spinal manipulation therapy (SMT) on the in vitro production of inflammatory cytokines, tumor necrosis factor alpha, and interleukin (IL) 1beta, in relation to the systemic (in vivo) levels of neurotransmitter substance P (SP).
Sixty-four asymptomatic subjects were assigned to SMT, sham manipulation, or venipuncture control group. SMT subjects received a single adjustment in the thoracic spine. Blood and serum samples were obtained from subjects before and then at 20 minutes and 2 hours after intervention. Whole-blood cultures were activated with lipopolysaccharide (LPS) for 24 hours. Cytokine production in culture supernatants and serum SP levels were assessed by specific immunoassays.
Over the study period, a significant proportion (P </= .05) of sham and control subjects demonstrated progressive increases in the synthesis of tumor necrosis factor alpha and IL-1beta. Conversely, in a comparable proportion of cultures from SMT-derived subjects, the production of both cytokines decreased gradually. Normalization of the observed alterations to reflect the changes relative to self-baselines demonstrated that, within 2 hours after intervention, the production of both cytokines increased significantly (P < .001 to .05) in both controls. In contrast, a significant (P < .001 to .05) reduction of proinflammatory cytokine secretion was observed in cultures from SMT-receiving subjects. In all study groups, serum levels of SP remained unaltered within 2 hours after intervention.
SMT-treated subjects show a time-dependent attenuation of LPS-induced production of the inflammatory cytokines unrelated to systemic levels of SP. This suggests SMT-related down-regulation of inflammatory-type responses via a central yet unknown mechanism.
... Total unique articles that meet criteria REFS** Autoimmune 0 n/a Blood Pressure 30 Cortisol 11 [76][77][78][79][80][81][82][83][84][85][86] Cytokine 12 [84,85,[87][88][89][90][91][92][93][94][95][96] Heart Rate Variability/HRV 29 [63,64,70,73, Immune/Immunity 27 [85,93,96, Interferon 2 [87,95] Interleukin 10 [84][85][86][87][90][91][92]95,137,138] Sleep 29 Substance P 4 [86,[175][176][177] Tumor Necrosis Factor/TNF 6 [88,89,92,95,96,178] Transforming Growth Factor/TGF 0 n/a ...
... Total unique articles that meet criteria REFS** Autoimmune 0 n/a Blood Pressure 30 Cortisol 11 [76][77][78][79][80][81][82][83][84][85][86] Cytokine 12 [84,85,[87][88][89][90][91][92][93][94][95][96] Heart Rate Variability/HRV 29 [63,64,70,73, Immune/Immunity 27 [85,93,96, Interferon 2 [87,95] Interleukin 10 [84][85][86][87][90][91][92]95,137,138] Sleep 29 Substance P 4 [86,[175][176][177] Tumor Necrosis Factor/TNF 6 [88,89,92,95,96,178] Transforming Growth Factor/TGF 0 n/a ...
... Total unique articles that meet criteria REFS** Autoimmune 0 n/a Blood Pressure 30 Cortisol 11 [76][77][78][79][80][81][82][83][84][85][86] Cytokine 12 [84,85,[87][88][89][90][91][92][93][94][95][96] Heart Rate Variability/HRV 29 [63,64,70,73, Immune/Immunity 27 [85,93,96, Interferon 2 [87,95] Interleukin 10 [84][85][86][87][90][91][92]95,137,138] Sleep 29 Substance P 4 [86,[175][176][177] Tumor Necrosis Factor/TNF 6 [88,89,92,95,96,178] Transforming Growth Factor/TGF 0 n/a ...
In this paper we synthesize an expansive body of literature examining the multifaceted influence of chiropractic care on processes within and modulators of the neuroendocrine-immune (NEI) system, for the purpose of generating an inductive hypothesis regarding the potential impacts of chiropractic care on integrated physiology. Taking a broad, interdisciplinary, and integrative view of two decades of research-documented outcomes of chiropractic care, inclusive of reports ranging from systematic and meta-analysis and randomized and observational trials to case and cohort studies, this review encapsulates a rigorous analysis of research and suggests the appropriateness of a more integrative perspective on the impact of chiropractic care on systemic physiology. A novel perspective on the salutogenic, health-promoting effects of chiropractic adjustment is presented, focused on the improvement of physical indicators of well-being and adaptability such as blood pressure, heart rate variability, and sleep, potential benefits that may be facilitated through multiple neurologically mediated pathways. Our findings support the biological plausibility of complex benefits from chiropractic intervention that is not limited to simple neuromusculoskeletal outcomes and open new avenues for future research, specifically the exploration and mapping of the precise neural pathways and networks influenced by chiropractic adjustment.
... Out of 15 studies [15,[18][19][20][21]35,36,[51][52][53][54][55][56][57][58], nine studies were RCTs with three groups [21,35,36,51,52,54,[56][57][58] five studies were RCTs with two groups [15,[18][19][20]55] and one study had four groups [53]. ...
... Out of 15 studies [15,[18][19][20][21]35,36,[51][52][53][54][55][56][57][58], nine studies were RCTs with three groups [21,35,36,51,52,54,[56][57][58] five studies were RCTs with two groups [15,[18][19][20]55] and one study had four groups [53]. ...
... The mean age of participants across all studies was 29.7 years. While 11 studies [15,20,21,35,51,[53][54][55][56][57][58] included both male and female participants; three studies [19,36,52] included only male participants; and one study [18] [18,20,53,58] included participants with pain (3 with neck pain and 1 with Achilles tendinopathy) and one study incuded participants with renal lithiasis. ...
Objective:
The aim of this systematic review was to update the current level of evidence for spinal manipulation in influencing various biochemical markers in healthy and/or symptomatic population.
Methods:
This is a systematic review update. Various databases were searched (inception till May 2023) and fifteen trials (737 participants) that met the inclusion criteria were included in the review. Two authors independently screened, extracted and assessed the risk of bias in included studies. Outcome measure data were synthesized using standard mean differences and meta-analysis for the primary outcome (biochemical markers). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of the body of evidence for each outcome of interest.
Results:
There was low-quality evidence that spinal manipulation influenced various biochemical markers (not pooled). There was low-quality evidence of significant difference that spinal manipulation is better (SMD -0.42, 95% CI - 0.74 to -0.1) than control in eliciting changes in cortisol levels immediately after intervention. Low-quality evidence further indicated (not pooled) that spinal manipulation can influence inflammatory markers such as interleukins levels post-intervention. There was also very low-quality evidence that spinal manipulation does not influence substance-P, neurotensin, oxytocin, orexin-A, testosterone and epinephrine/nor-epinephrine.
Conclusion:
Spinal manipulation may influence inflammatory and cortisol post-intervention. However, the wider prediction intervals in most outcome measures point to the need for future research to clarify and establish the clinical relevance of these changes.
... In addition, some touch-based interventions, like manual therapy, can influence the interaction between inflammatory mediators and peripheral nociceptors by modulating the concentration of inflammatory and pain-related mediator substances [23]. For instance, Teodorczyk-Injeyan et al. [75] found a 20% reduction in cytokine concentration (e.g., tumor necrosis factor-TNFα and interleukine 1 beta-IL-1β), which lasted for about 2 hours after a specific manual technique. However, the exact mechanisms and effectiveness of these therapies are still under investigation and remain a topic of ongoing research and debate [25,41,47]. ...
The evidence on how touch-based therapy acts on the brain activity opens novel cues for the treatment of chronic pain conditions for which no definitive treatment exists. Touch-based therapies, particularly those involving C-tactile (CT)-optimal touch, have gained increasing attention for their potential in modulating pain perception and improving psychological well-being. While previous studies have focused on the biomechanical effects of manual therapy, recent research has shifted towards understanding the neurophysiological mechanisms underlying these interventions. CT-optimal touch, characterized by gentle stroking that activates CT afferents, may be used to reduce pain perception in chronic pain conditions and to enhance psychological well-being. Further research is needed to fully elucidate the neurophysiological mechanisms involved and to establish the therapeutic efficacy of CT-optimal touch in various clinical populations.
... SMT can affect the interaction of inflammation thanks to peripheral mediators and nociceptors that occur after tissue injury by modifying the concentration of substances that mediate inflammation and pain (19). ...
Background: Cervical pain is one of the most common pathologies in physiotherapy consultations. Currently, there are countless techniques, protocols, and treatments ranging from conservative to invasive. The intervention includes orthopedic manual therapy techniques in patients who present the pathology. To date, several studies apply spinal manipulation as a treatment option for patients with neck pain; however, its effects on pain and disability are unknown. Methodology: A compilation, selection, and analysis of randomized clinical trials was carried out, and studies showed the effect of this technique on the type and origin of pain in patients with neck pain. Data extraction was formulated in tables, and the methodological quality was determined through the physiotherapy evidence database scale. Results: Thirty studies were included that were classified based on the type and origin of pain. In order to determine the effectiveness, it was applied as the only treatment technique or as part of a multimodal treatment. Conclusions: Spinal manipulation has a greater effect on pain and disability when considered as the only treatment technique in patients with acute pain. However, when applied as part of the multimodal protocol, it proves to be effective in chronic, radicular, mechanical, and nonspecific pain. The high heterogeneity of the studies is a limitation of our findings. Keywords: spinal manipulation, neck pain, cervical vertebral, acute pain, chronic pain. Resumen Antecedentes: El dolor cervical es una de las patologías más comunes presente en la consulta de fisioterapia, en la actualidad existen un sin número de técnicas, protocolos y tratamientos que van desde lo conservador hasta lo invasivo, en la intervención se incluye técnicas de terapia manual ortopédica en pacientes que presentan la patología antes mencionada. Hasta la fecha, existen varios estudios que aplican manipulación espinal como opción de tratamiento para pacientes con dolor cervical, sin embargo, se desconocen sus efectos sobre dolor y la discapacidad. Metodología: se realizó la recopilación, selección y análisis de ensayos clínicos aleatorizados que en sus estudios se evidenció el efecto de esta técnica sobre el tipo y origen del dolor en pacientes con cervicalgia, la extracción de datos se formuló en tablas; la calidad metodológica fue determinada a través de la escala de Physiotherapy Evidence Database, Resultados: se incluyeron treinta estudios que fueron clasificados en base al tipo y origen del dolor, para determinar la efectivad, se tomó en cuenta si era aplicada como única técnica de tratamiento o siendo parte de un tratamiento multimodal. Conclusiones: la manipulación espinal tiene mayor eficacia sobre el dolor y la discapacidad al ser considerada como única técnica de tratamiento en pacientes con dolor agudo; sin embargo, cuando es aplicada como parte del protocolo multimodal demuestra ser eficaz en el dolor crónico, radicular, mecánico e inespecífico, la alta heterogeneidad de los estudios es una limitante para nuestros hallazgos. Palabras Clave: manipulación espinal, cervicalgia, vértebras cervicales, dolor agudo, dolor crónico.
... Regarding treatments, orthopedic manual physical therapy (OMPT) has traditionally been one of the most interesting therapeutic options for LBP. It is important to mention that the effects of OMPT have been found to be mainly short term [8,9]. Furthermore, neural mobilization, which is within the scope of OMPT techniques, can also be an effective tool for short term improvements in LBP patients [10,11]. ...
Low back pain and its chronification are among the most common causes of disabilities worldwide. This is why multiple interventions and treatment approaches have been investigated around this pathology in recent years. Currently, the evidence is increasingly leaning towards treating chronic low back pain with a treatment based on the patient's centered biopsychosocial model. This case report presents the evaluation and treatment of a 43-year-old woman with chronic low back pain using a multimodal physiotherapy based on a biobehavioral approach. In the physiotherapy intervention, the patient's pain characteristics and somatosensory, motor-functional, and affective-cognitive states were first evaluated. Subsequently, a multimodal treatment including therapeutic exercise, pain neuroscience education, and orthopedic manual and physical therapies was applied for a total of 14 sessions over a period of 9 weeks. Finally, a post-intervention evaluation and at the one-month follow-up were carried out, in which it was observed that the treatment had significantly improved the patient's symptomatology and their general state. This case suggests that a multimodal physiotherapy treatment based on a biobehavioral approach is an effective option to improve pain symptoms and somatosensory, motor-functional, and affective-cognitive aspects in the reported patient; therefore, a treatment of these characteristics may be an option for patients with chronic low back pain.
... It is now commonly accepted that SM can influence various mechanisms at the peripheral, spinal, and supraspinal levels [1,4,5]. Further, evidence also demonstrates systemic effects of SM like anti-inflammation [6] and changes in biochemical markers such as substancep, cortisol and neurotensin [5]. Importantly, there is consensus within manual therapy researchers/clinicians that SM may influence the autonomic nervous system (ANS) [7][8][9]. ...
Background:
Spinal manipulation (SM) has been hypothesized to influence the autonomic nervous system (ANS). Further, it has been proposed that the effects may vary depending on the segment manipulated. The aim of this systematic review was to synthesize the current level of evidence for SM in influencing the ANS in healthy and/or symptomatic population.
Methods:
Various databases (n = 8) were searched (inception till May 2023) and 14 trials (n = 618 participants) were included in the review. Two authors independently screened, extracted and assessed the risk of bias in included studies. The data were synthesized using standard mean differences and meta-analysis for the primary outcome measures. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of the body of evidence for each outcome of interest.
Results:
Overall, there was low quality evidence that SM did not influence any measure of ANS including heart rate variability (HRV), oxy-hemoglobin, blood pressure, epinephrine and nor-epinephrine. However, there was low quality evidence that cervical spine manipulation may influence high frequency parameter of HRV, indicating its influence on the parasympathetic nervous system.
Conclusion:
When compared with control or sham interventions, SM did not alter the ANS. Due to invalid methodologies and the low quality of included studies, findings must be interpreted with great caution. Future studies are needed which employ rigorous data collection processes to verify the true physiological implications of SM on ANS.
The review discusses the pathogenetic mechanisms of primary osteoarthritis (OA) formation. The recommendations of the Association of Rheumatologists of Russia on the main principles of rehabilitation for OA are presented, including drug and non-drug methods of pain syndrome correction, improvement of motor activity and quality of life of patients. Particular attention is paid to the mechanisms of osteopathic correction for OA, which are aimed at restoring the impaired biomechanics of the patient’s body, eliminating persistent muscle hypertonicity, peripheral sensitization, and aimed at regulating antinociceptive mechanisms. An important advantage of manual treatment is the possibility of its use before, during or after other types of treatment and the ability to enhance their therapeutic potential.
Mobilisation and manipulation techniques can be found in both Western and Chinese medicine. It is worth taking a comparative look at these techniques and how they work. The article compares mobilising Tuina techniques with osteopathic techniques and uses the examples of the treatment of the sacroiliac joint, the hip and the knee to illustrate the findings.
Osteopathy in Russia has now formed as an independent direction of scientific knowledge and has all three characteristic levels – general philosophical, general scientific and specific scientific, as well as its own methodology. The following had been done in osteopathy as in a scientific direction of medicine: 1) its own conceptual apparatus was created; 2) a methodology had been developed that allows the use of evidence-based medicine approaches and mathematical processing of the results obtained; 3) scientific knowledge has a systematic, ordered nature; 4) the object, subject and content of osteopathy as a scientific direction were determined; 5) experimental and clinical evidence of the effectiveness of osteopathic treatment for various diseases and health disorders had been obtained. When conducting clinical studies in osteopathy, a wide range of methods for examining patients is used to obtain reliable information about the condition of organs and tissues, as well as about the body as a whole. Still it is necessary to develop the scientific component of osteopathy more actively, conduct multicenter clinical research to study clinical effectiveness, develop methodological and organizational foundations for providing osteopathic care to various groups of the population with somatic dysfunctions at all stages (prevention, diagnosis, treatment and medical rehabilitation) in order of preservation of human health, prevention of common non-communicable diseases, medical rehabilitation of patients after serious illnesses.
Background
Matching disease and treatment mechanisms is a goal of the Precision Medicine Initiative. Pro- and anti-inflammatory cytokines (e.g., Tumor Necrosis Factor-alpha, Transforming Growth Factor-beta, and Interleukin-2, 10, and 12) have gained a significant amount of interest in their potential role in persistent pain for musculoskeletal (MSK) conditions. Manual therapy (MT) and exercise are two guideline-recommended approaches for treating MSK conditions. The objective of this narrative overview was to investigate of the effects of MT and exercise on pro- and anti-inflammatory cytokines and determine the factors that lead to variability in results.
Methods
Two reviewers evaluated the direction and variabilities of MT and exercise literature. A red, yellow, and green light scoring system was used to define consistencies.
Results
Consistencies in responses were seen with acute and chronic exercise and both pro- and anti-inflammatory cytokines. Chronic exercise is associated with a consistent shift towards a more anti-inflammatory cytokine profile (Transforming Growth Factor-beta, and Interleukin-2 and 13, whereas acute bouts of intense exercise can transiently increase pro-inflammatory cytokine levels. The influence of MT on cytokines was less commonly studied and yielded more variable results.
Conclusion
Variability in findings is likely related to the subject and their baseline condition or disease, when measurement occurs, and the exercise intensity, duration, and an individual's overall health and fitness.
This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed.
It is widely presumed that in addition to CD14, other molecules are necessary for lipopolysaccharide (LPS)-induced cell activation. In order to shed light on some of the biological and biochemical properties of these molecules, we examined the LPS responsiveness of CD14-negative, ST2 cells. Although ST2 cells do not express CD14 mRNA, they, nonetheless, expressed IL-6 mRNA and synthesized IL-6 protein when incubated with LPS in serum-free medium (i.e. without soluble CD14). Paxlitacel (Taxol™) also induced IL-6 mRNA expression in ST2 cells, while Rhodobacter sphaeroides diphoshoryl lipid A (RsDPLA) inhibited both LPS- and Taxol-induced expression of IL-6 mRNA. Collectively, these data suggest that LPS, RsDPLA, and Taxol all recognize the same receptor complex on ST2 cells and do not require the participation of CD14. In addition, using antibody raised against the ST2 cell membrane fraction, we detected a set of LPS-specific membrane antigens in murine peritoneal macrophages, including two designated p57 (57 kDa) and p53 (53 kDa). There was no qualitative difference in the expression of p57 and p53 in LPS-responsive, C3H/HeN and LPS-hyporesponsive, C3H/HeJ macrophages. However, after stimulating the macrophages with LPS or Taxol, expression of p57 and p53 was diminished in C3H/HeN macrophages, but not in C3H/HeJ macrophages. Phorbol ester (PMA) and A23187 calcium ionophore did not suppress p57 or p53 expression, and the lipid A precursor, PE406, did not bind to either protein. Thus, p57 and p53 may play important roles in LPS-evoked responses, but they do not appear to serve as LPS receptors.
Monocytes from different individuals show variable cytokine production in response to a variety of stimuli. We wished to determine the sets of conditions (cytokine combinations) that would enable us to demonstrate stable inter-individual differences in the production of IL-1α, IL-1β, IL-1Ra, IL-6 and tumour necrosis factor-alpha (TNF-α) by monocytes. We assessed the ability of a number of recombinant human cytokines (granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-γ), TNF-α, IL-4, IL-6, transforming growth factor-beta (TGF-β), IL-10 and IL-1Ra) to stimulate or inhibit the production of one or more of these monocyte products. GM-CSF was found to stimulate the production of all five of these cytokines in a highly reproducible manner. TNF-α also up-regulated production of IL-1α, IL-1β, IL-1Ra and IL-6 by monocytes, but the variability in the results of cells cultured from the same individuals on different occasions was greater. Other cytokines either stimulated production of only some of the five cytokine products tested, or stimulated the production of some cytokine products while inhibiting production of others. This was especially evident when cytokines were used in combination with GM-CSF: IFN-γ down-regulated production of IL-1Ra while up-regulating the production of IL-1α/β, IL-6 and TNF-α, while IL-4 had the exact opposite effect. Polymorphisms in regions of cytokine genes that affect transcription may account for some of the inter-individual variation in cytokine production. We have shown that a stable estimate of cytokine production phenotype can be obtained when monocytes collected on at least two separate occasions are stimulated by GM-CSF in vitro. We have looked for a relationship between IL-1 production and an 86-bp variable repeat polymorphism in intron 2 of the IL-1Ra gene. A less common allele of this polymorphism (allele 2) was associated with increased production of IL-1Ra protein, and also reduced production of IL-1α protein by monocytes.
The effect of spinal manipulation on the respiratory burst of polymorphonuclear neutrophils (PMN) and monocytes from treated adults was measured by zymosan-stimulated chemiluminescence (CL). Peripheral blood was collected 15 min before and 15 min after treatment (sham manipulation, thoracic spine manipulation, or soft tissue manipulation), the cells were isolated, challenged with a standardized, opsonized luminol-containing suspension of zymosan, and monitored for CL. Plasma from two subsets of subjects was radioimmunoassayed for Substance P (SP). PMN were also preincubated with SP in vitro over the dose range 5 x 10(-12) M to 5 x 10(-8) M and the CL response monitored. The CL responses of both PMN and monocytes from subjects who received spinal manipulation were significantly higher after than before treatment, and significantly higher than the response in sham or soft-tissue treated subjects. Measurement of the force applied by sham and spinal manipulation suggested a force threshold for the enhancement of the CL response. Plasma levels of SP before and after treatment in sham treated subjects did not differ significantly; however, elevated plasma SP was observed in subjects after spinal manipulation. Preincubation of PMN with 1 x 10(-11) M, 5 x 10(-11) M or 1 x 10(-10) M SP in vitro primed PMN for an enhanced respiratory burst when the cells were subsequently challenged
A critical need in assessing the clinical utility of manipulative therapy for back pain is the identification of biological changes associated with the forces applied by spinal manipulation. Such changes could then serve as markers for both sham treatment and manipulation. We determined the priming of polymorphonuclear neutrophils for an enhanced respiratory burst and its duration, the priming of mononuclear cells for enhanced endotoxin-stimulated tumor necrosis factor production and plasma levels of substance P following a single thoracic spine manipulation. There was a significant difference in the respiratory burst of polymorphonuclear neutrophils in response to a particulate challenge, depending on the time of blood sample collection. The response of polymorphonuclear neutrophils isolated from blood collected 15 min after manipulation was significantly higher than the response of cells isolated from blood collected 15 min before and 30 and 45 min after manipulation. Mononuclear cells were also primed for enhanced endotoxin-stimulated tumor necrosis factor production by spinal manipulation. Both of these priming effects were accompanied by a slight, but significant elevation in plasma substance P. The mean manipulation force associated with these biological effects was 878 +/- 99 N. These biological effects may provide a means of monitoring the delivery of both sham and manipulative treatment and, therefore, provide a crucial tool for understanding the efficacy of manipulative therapy