Recent concepts in the neurophysiology of pain

doi:10.1054/math.1999.0207

Manual Therapy

Volume 4, Issue 4, November 1999, Pages 196-202

https://doi.org/10.1054/math.1999.0207 Get rights and content

Abstract

This paper describes many of the processes that exist for upregulation of the nociceptive system in response to tissue injury. The processes of peripheral and central sensitization are described. Potential interactions between the nociceptive, motor and autonomic systems are considered. The potential for psychosocial factors to influence neuroplasticity within the nociceptive system is also discussed.

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Therapeutic ultrasound ameliorates hyperalgesia and edema on CFA-induced persistent inflammatory response in mice
2023, Brazilian Journal of Anesthesiology (English Edition)
Citation Excerpt :
There are different stimuli to induce the inflammatory process in the mice's paw, such as the Complete Freund's Adjuvant (CFA), which acts as an irritative agent.6,7 This inflammatory response induces edema, increase of tissue volume, and consequent hypersensitivity to thermal and mechanical stimuli,6-8 which is due to changes on the production of peripheral inflammatory mediators, thereby facilitating prolonged depolarization of the neuronal membrane and exacerbating hyperalgesia or allodynia.9 Besides drug therapy, therapeutic ultrasound action in inflammatory treatment has been investigated by different studies, which include the use of US and other resources for inflammatory response control and consequent inhibition of edema and pain.10
The present study investigated the effects of pulsed and continuous ultrasound (USP and USC) in edema and hyperalgesia after chronic inflammatory process induced by Complete Freund's Adjuvant-CFA and analyzing the relationship of the application frequency of ultrasound, in pro- and anti-inflammatory cytokine production.
Forty-five animals were divided into 9 groups; all animals from groups 2 to 9 were subjected to a persistent inflammation model induced by CFA in mice. We report the effects and the underlying action mechanisms of USP and USC in the animals which were irradiated two, three or five times a week on the left hind paw. The analyses performed in this study were: evaluation of hind paw edema through the plethysmometer, evaluation of thermal hyperalgesia through withdrawal test using a water container at 44.5°C (± 0.5°C), and the plantar region of the left paw which was removed for analysis of cytokines.
Our results showed that USP and USC consistently reduced paw edema, and pulsed ultrasound showed a higher significant effect than the continuous mode. Moreover, groups with irradiation frequency of five times a week presented an inhibition of the edema, and groups with frequency of three or two times a week reduced mainly hyperalgesia, in comparison with the control group. The beneficial effects of the US then seem to be associated with upregulation of anti- and pro-inflammatory mediators, such as IL-10 and IL-6, respectively.
This study provided evidence that ultrasound constitutes an important non-pharmacological intervention for the management of inflammatory and pain states.
The physiology of manual therapy
2021, A Comprehensive Guide to Sports Physiology and Injury Management: An Interdisciplinary Approach
Effect of spinal manipulation thrust magnitude on trunk mechanical activation thresholds of lateral thalamic neurons
2014, Journal of Manipulative and Physiological Therapeutics
High-velocity low-amplitude spinal manipulation (HVLA-SM), as performed by doctors who use manual therapy (eg, doctors of chiropractic and osteopathy), results in mechanical hypoalgesia in clinical settings. This hypoalgesic effect has previously been attributed to alterations in peripheral and/or central pain processing. The objective of this study was to determine whether thrust magnitude of a simulated HVLA-SM alters mechanical trunk response thresholds in wide dynamic range (WDR) and/or nociceptive specific (NS) lateral thalamic neurons.
Extracellular recordings were carried out in the thalamus of 15 anesthetized Wistar rats. Lateral thalamic neurons having receptive fields, which included the lumbar dorsal-lateral trunk, were characterized as either WDR (n = 22) or NS (n = 25). Response thresholds to electronic von Frey (rigid tip) mechanical trunk stimuli were determined in 3 directions (dorsal-ventral, 45° caudalward, and 45° cranialward) before and immediately after the dorsal-ventral delivery of a 100-millisecond HVLA-SM at 3 thrust magnitudes (control, 55%, 85% body weight).
There was a significant difference in mechanical threshold between 85% body weight manipulation and control thrust magnitudes in the dorsal-ventral direction in NS neurons (P = .01). No changes were found in WDR neurons at either HVLA-SM thrust magnitude.
This study is the first to investigate the effect of HVLA-SM thrust magnitude on WDR and NS lateral thalamic mechanical response threshold. Our data suggest that, at the single lateral thalamic neuron level, there may be a minimal spinal manipulative thrust magnitude required to elicit an increase in trunk mechanical response thresholds.
Back pain in space and post-flight spine injury: Mechanisms and countermeasure development
2013, Acta Astronautica
Citation Excerpt :
The mechanism of lumbar back pain relief in the central nervous system is probably through a neutralization of nociceptive neurotransmitters in the dorsal horn of the spinal cord [96]. Substance P and Neurokinin A are the nociceptive neurotransmitters released at the pre-synaptic terminals in response to nerve impulses from peripheral nociceptive fibres and neurochemicals that can suppress the effects of nociceptive neurotransmitters are called endocoids or opioids [96,114]. Enkephalins and endorphins are a class of opioid neurotransmitters which have analgesic effects and released centrally in the spinal cord via stimulation of peripheral mechanoreceptors Type I (Ruffini corpuscles) and Type II (Paccinian corpuscles) embedded in the substance of collagen fibres of ligaments, facet joint capsule, and myofascia [96].
During spaceflight many astronauts experience moderate to severe lumbar pain and deconditioning of paraspinal muscles. There is also a significant incidence of herniated nucleus pulposus (HNP) in astronauts post-flight being most prevalent in cervical discs. Relief of in-flight lumbar back pain is facilitated by assuming a knee-to-chest position. The pathogenesis of lumbar back pain during spaceflight is most likely discogenic and somatic referred (from the sinuvertebral nerves) due to supra-physiologic swelling of the lumbar intervertebral discs (IVDs) due to removal of gravitational compressive loads in microgravity. The knee-to-chest position may reduce lumbar back pain by redistributing stresses through compressive loading to the IVDs, possibly reducing disc volume by fluid outflow across IVD endplates. IVD stress redistribution may reduce Type IV mechanoreceptor nerve impulse propagation in the annulus fibrosus and vertebral endplate resulting in centrally mediated pain inhibition during spinal flexion. Countermeasures for lumbar back pain may include in-flight use of: (1) an axial compression harness to prevent excessive IVD expansion and spinal column elongation; (2) the use of an adjustable pulley exercise developed to prevent atrophy of spine muscle stabilisers; and (3) other exercises that provide Earth-like annular stress with low-load repetitive active spine rotation movements. The overall objective of these countermeasures is to promote IVD health and to prevent degenerative changes that may lead to HNPs post-flight. In response to “NASA’s Critical Path Roadmap Risks and Questions” regarding disc injury and higher incidence of HNPs after space flight (Integrated Research Plan Gap-B4), future studies will incorporate pre- and post-flight imaging of International Space Station long-duration crew members to investigate mechanisms of lumbar back pain as well as degeneration and damage to spinal structures. Quantitative results on morphological, biochemical, metabolic, and kinematic spinal changes in the lumbar spine may aid further development of countermeasures to prevent lumbar back pain in microgravity and reduce the incidence of HNPs post-flight.
Topographical pressure and thermal pain sensitivity mapping in patients with unilateral lateral epicondylalgia
2011, Journal of Pain
Citation Excerpt :
Further, the present findings, ie, heterogeneous pressure hyperalgesia on muscle belly and musculotendinous junctions are likely to be explained by differences in muscle thickness,3 density of groups III and IV afferents,4 or different concentrations of inflammatory mediators such as amino acids, neuropeptides, or cytokines.38 Thus, these changes may increase the excitability of wide-dynamic range neurons and increase receptive field size51 as depicted by the pressure pain topographical maps. The presence of cold and heat hyperalgesia in individuals with LE is still a matter of debate, as some studies have not found thermal hyperalgesia over the lateral epicondyle in patients with LE47,52 whereas a recent study challenged this finding.16
Our aim was to quantify spatial differences in pressure and thermal pain sensitivity maps between patients with unilateral lateral epicondylalgia (LE) and age- and sex-matched controls. Pressure (PPT), cold (CPT), and heat (HPT) pain thresholds were assessed over 12 points forming a 3 × 4 matrix (4 points in the superior part, 4 points in the middle, and 4 points in the lower part around the lateral epicondyle) bilaterally in 16 subjects with strictly unilateral LE and 16 age- and sex-matched controls in a blinded design. Topographical pain sensitivity maps to pressure and thermal stimulation over the elbow in patients with LE and healthy controls were calculated. A multilevel 3-way ANCOVA test was applied to detect differences in topographical maps between groups. Subjects with LE showed bilateral lower PPT, higher CPT (pain at higher temperature) and lower HPT (pain at lower temperature) at all the measurement points as compared to controls (all, P < .01). PPT were lower at points over the extensor carpi radialis brevis (ECRB) muscle as compared to points over the extensor digitorum communis muscle (P < .01) and over the extensor carpi ulnaris muscle (P < .001). CPT and HPT were not significantly different between points (P > .05). Topographical pressure and thermal pain sensitivity maps revealed bilateral hyperalgesia in patients with strictly unilateral LE. LE patients exhibited heterogeneously distributed pressure pain hyperalgesia while cold or heat maps were homogenous. The most sensitive localizations for PPT assessment corresponded to the muscle belly of the ECRB. Our results confirm the role of ECRB muscle in LE and argue for evidence of peripheral and central sensitization mechanisms in patients with strictly unilateral symptoms.
Topographical pressure and thermal sensitivity maps revealed bilateral hyperalgesia in patients with strictly unilateral lateral epicondylalgia (LE). LE patients exhibited heterogeneously distributed pressure pain hyperalgesia while cold or heat pain maps were homogenous. The most sensitive localizations for PPT assessment corresponded to the muscle belly of the ECRB.
An investigation into the effects of a unilaterally applied lumbar mobilisation technique on peripheral sympathetic nervous system activity in the lower limbs
2008, Manual Therapy
Citation Excerpt :
Although, the last two decades have seen the emergence of conceptual models supporting the use of SMT in the management of segmental pain and joint dysfunction (Zusman, 1986, 2004; Wright, 1995). Hypothetical mechanisms of action of SMT include: direct physiological effects on articular and peri-articular structures (Wyke and Polacek, 1975), neurophysiological mechanisms at both spinal and supraspinal levels (Wright, 1995, 1999; Solly, 2004), endocrine/hormonal effects and a non-specific placebo effect (Zusman, 1986, 2004; Katavich, 1998). The dilemma facing the clinician, in determining the physiological and therapeutic effects of SMT interventions on patients, is the difficulty in accurately and quantitatively measuring the proposed effects on the key target tissue.
Physiotherapeutic management of lumbar disorders often utilises specific segmental joint mobilisation techniques; however, there is only limited evidence of any neurophysiological effects and much of this has focused on the cervical spine and upper limbs. This study aims to extend the knowledge base underpinning the use of a unilaterally applied lumbar spinal mobilisation technique by exploring its effects on the peripheral sympathetic nervous system (SNS) of the lower limbs.
Using a double blind, placebo controlled, independent groups study design and based upon power calculations, 45 normal naïve healthy males were randomly assigned to one of three experimental groups (control, placebo or treatment; a unilaterally applied postero-anterior mobilisation to the left L4/5 zygopophyseal joint). SNS activity was determined by recording skin conductance (SC) obtained from lower limb electrodes connected to a BioPac unit. Validation of the placebo technique was performed by post-intervention questionnaire. Results indicated that there was a significant change in SC from baseline levels (13.5%) that was specific to the side treated for the treatment group during the intervention period (compared to placebo and control conditions).
This study provides preliminary evidence that a unilaterally applied postero-anterior mobilisation technique performed, at a rate of 2 Hz, to the left L4/5 lumbar zygopophyseal joint results in side-specific peripheral SNS changes in the lower limbs.

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^f1: Anthony Wright BSc(Hons) Phty. Grad Cert Ed, Mphty St (Manip Ther), PhD, School of Medical Rehabilitation, Faculty of Medicine, University of Manitoba, T258–770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E OW3.

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Review articleRecent concepts in the neurophysiology of pain

Abstract

British Journal of Anaesthesia

Pain

Pain

Brain Research

British Journal of Anaesthesia

Brain Research

Neuroscience

Neuroscience Research

Medical Hypotheses

Pain

Pain

British Journal of Anaesthesia

Pain

British Journal of Anaesthesia

Pain

Pain

British Journal of Anaesthetics

Neuroscience

Sympathetically maintained pain – a unifying hypothesis

Review article
Recent concepts in the neurophysiology of pain