Research Review By Dr. Brynne Stainsby©


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Date Posted:

February 2020

Study Title:

Diverse role of biological plasticity in low back pain and its impact on sensorimotor control of the spine


Hodges PW, Barbe MF, Loggia ML, Nijs J & Stone LS

Author's Affiliations:

Clinical Centre for Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia; Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; Pharmacology and Therapeutics and Department of Anesthesiology, McGill University, Montreal, Canada; Alan Edwards Centre for Research on Pain, Faculty of Dentistry and Faculty of Medicine, McGill University, Montreal, Canada.

Publication Information:

Journal of Orthopaedic & Sports Physical Therapy 2019; 49(6): 389-401.

Background Information:

It is commonly believed that pain and injury are complex processes, leading to multi-system adaptation beyond changes in neural excitation, inhibition and processing. While ‘plasticity’ is a term commonly ascribed to the nervous system, ‘biological plasticity’ is a broader term that has been used to capture the number of biological processes that undergo change in the presence of pain and shape the response of the individual. Pain is no longer considered simply the response to nociceptive stimuli, it requires the understanding of different underlying mechanisms, activation of neural systems (beyond simply the nociceptive neurons), the interactions of the neural and immune systems, tissue changes and the implications on the psychological and social domains. All of these systems have a potential role in the sensorimotor adaptations to pain, as well as the potential for the maintenance of the pain response.

The goal of this commentary is to present a current view of the implications of the biology of pain and injury for sensorimotor function, particularly in the spine.


Contemporary View of Biology of Pain:

While pain is an individualized experience, there are some consistent underlying biological mechanisms, which affect the sensorimotor control of the spine. Below the common mechanistic descriptors are outlined:
  • Nociceptive pain (may also be referred to as “pain associated with ongoing nociceptive input”) is defined as pain that is experienced with real or threatening damage to nonneuronal tissues and is driven by the activation of the nociceptors (1). It is typically not evaluated clinically, but the term is commonly used to describe pain that is considered “proportional” to the input, and present within a normally functioning somatosensory system (1-3).
  • Neuropathic pain is defined as pain associated with a lesion or disease of the somatosensory nervous system (1).
  • In many patients, a clear origin is lacking or not severe enough to explain the pain experienced by the patient, and there is no evidence of damage/disease in the somatosensory nervous system. This is often explained by the concept of central sensitization(4), broadly defined as “an amplification of neural signalling within the central nervous system (CNS) that elicits pain hypersensitivity” (5) or “increased responsiveness of nociceptive neurons in the CNS to their normal or subthreshold input” (1). This is a common descriptor for chronic pain states. It should be noted that central pain (6), centralized pain (7) or central sensitization pain (8, 9) are terms that are often used interchangeably, but do not necessarily refer to the neurophysiological process of sensitization. The related term nociplastic has been defined by the International Association for the Study of Pain to describe “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain” (10).
  • Central sensitization can be demonstrated by altered sensory processing, including increased activity of brain-orchestrated nociceptive faciliatory pathways (11), poor functioning of descending antinociceptive mechanisms (12), and increased activity of brain-orchestrated nociceptive facilitatory pathways (11). Clinically, psychological attributes (such as fear of pain or catastrophizing) are common, and can affect sensitization.
  • Patients may also present with mixed presentations of chronic pain, and there is some evidence that a group of patients may have predominantly psychogenic pain, and present mainly with maladaptive, illness behaviours (8).
  • The presentation and relevance of sensorimotor features may differ between nociceptive, neuropathic and nociplastic/central pain, and likely require different approaches to management and rehabilitation. For example, tailoring treatment to optimise loading by rehabilitating the motor control system would be important for those with nociceptive pain, while those with nociplastic/central pain may require cognition-targeted exercises with pain neuroscience education (13, 14).
Neuroimmune Interactions in the Nervous System:
  • It is believed neuronal mechanisms are likely critical in the development of chronic pain, and in the past decade, animal research has highlighted the role glial cells may play in the development/maintenance of persistent pain conditions (15-17).
  • In the presence of a pain-initiating event such as an injury, microglia and astrocytes because “activated” (16,17) and upregulate the expression of receptors, increase the release of enzymes, inflammatory mediators, proinflammatory cytokines and chemokines, which sensitize the neural pathways involved in pain (18). In the acute phase, this can be protective as it limits further damage and promotes healing, however, if the activation is recessive or does not dissipate after the injury, glial activation creates a “pain produces pain” loop and is believed to be a critical event in central sensitization.
  • Pain-related neuroinflammation has been observed in the spinal cord (16) and sensory ganglia (19) and recently, has been discovered in the brain as well (20-25).
  • Recent human studies have provided in vivo evidence that glial cells may have a role in human LBP, using positron emission tomography (PET) scans to identify increased tracer binding in regions of the brain in those with chronic low back pain (26).
  • In another human study, authors found increased signals in the spinal cord of those with lumbar radiculopathy and noted the amount of inflammation predicted the amount of perceived relief after epidural steroid injection (27). Further research is required to better interpret results, but these findings do suggest the role of the neural system in the dysfunction related to the sensorimotor control of the spine.
  • Glial cells may also influence the availability of neurotransmitters (28), remove unused synapses and release molecules that regulate neuron structure, function and connectivity (29). It is therefore plausible that glial activation may play a role in modified motor and sensory function in those with persistent pain. This hypothesis has the potential to inform therapy; both pharmacological interventions and possibly even exercise to moderate glial activation.
Neuroimmune Interaction in the Somatic Tissues:
  • In the musculotendinous tissues, the role of the immune system is to phagocytose injured cells. The release of immune mediators sensitize the primary afferent terminals and increase vascular permeability. Typically, these are short-lived, reversible markers of acute inflammation but if the tissue does not have the opportunity to complete the healing process, persistent/chronic inflammation may develop (30).
  • At the cellular level, chronic inflammation is characterized by the prolonged presence of macrophages in/around tissues, which may contribute to secondary tissue damage.
  • In animal studies, the prolonged presence of inflammatory cytokines can lead to the production of an even greater number of cytokines and chemokines, increase the permeability of vessel walls, promote fibrosis and sensitize primary afferent terminals (increasing pain) (31-33). It is also possible that inflammatory cytokines can enter the blood stream and lead to systemic inflammatory effects, tissue damage and pain hypersensitivity (31). The pain-related neuropeptide, substance P, is produced by both neurons and peripheral immune cells, and can be linked to peripheral immune responses, central sensitization and enhanced pain behaviours in animals, though further research regarding its effects on humans is required. It is possible that substance P release may impact structural changes in back muscles of those with LBP (though this data is not yet published).
  • Peripheral immune system changes have possible relevance regarding the sensorimotor control of the spine. Sensitization decreases the threshold for nociceptor discharge (32) and may lead to increased muscle guarding. Tissue changes are also likely to impact muscle control and may limit or distort movement. Exercise can theoretically impact immune system activity and reverse tissue changes, however, the appropriate time course and movement specifics must be carefully determined.
Brain and Peripheral Tissue Interaction:
  • Mouse models have suggested that age-related intervertebral disc (IVD) degeneration increases disc innervation loss of disc height, muscle inflammation, sensory neuron plasticity and neuroinflammation in the spinal cord, which may contribute to chronic LBP (34-37). Interestingly, providing animals with a running wheel for several months attenuated behavioural indices of pain and histological/biochemical signs of disc pathology (unpublished data).
  • If peripheral structures such as the IVD contribute to chronic LBP, and the brains of those who have chronic pain are different from pain-free controls, it is important to consider whether chronic pain drives brain changes, or if there may be cortical features that could predispose one to chronic pain. In rats, it appears that peripheral input drove CNS pathology, however future research is required. In humans, subjects with chronic LBP underwent functional MRI, and changes in the prefrontal cortex and function both improved as subjects reported improvement in pain and disability (38,39). In contrast, in another study of subjects with chronic LBP, subjects who responded well to conservative treatment did not demonstrate any gray matter morphological changes (40). Further research is required.
  • Peripheral nociceptive input mediated by suboptimal sensorimotor control of the spine can cause and maintain maladaptive brain structural and functional changes. Combination of pharmacological and nonpharmacological interventions that target peripheral inputs from the spine and pathological CNS plasticity should be considered.

Clinical Application & Conclusions:

This body of literature is in its early stages, however, this commentary summarized the impact of biological processes on the pain experience and sensorimotor control. It highlighted the importance of considering targeted interventions to address both peripheral input and CNS plastic changes and identified the potential opportunity for exercise therapy to impact pain. Importantly however, the authors identified that further research is required before identifying specific clinical recommendations.

Study Methods:

This was a clinical commentary that did not report methodology.

Study Strengths / Weaknesses:

  • This commentary summarizes theoretical constructs related to the biological plasticity in a well-organized, well-described manner.
  • The authors carefully identify the limitations in the literature, particularly animal models and unpublished research, and caution readers from drawing unsupported conclusions.
  • The authors helpfully identify the fact that this field literature is characterized by inconsistency in findings.
  • Clinical suggestions for multimodal treatment approaches are provided.
  • The greatest weakness of this study is the lack of methodology reported. Without this, we cannot be confident that the conclusions were not subject to high risk of bias.
  • While this article provides a summary of the literature included, there is no formal assessment of the methodology or research quality. The authors included a number of unpublished and animal studies.
  • There is no comment on the participants or clinical setting of the included studies, thus limiting the external validity of the review.

Additional References:

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