scholarly journals What goes up must come down: insights from studies on descending controls acting on spinal pain processing

2019 ◽  
Vol 127 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Stevie Lockwood ◽  
Anthony H. Dickenson
Keyword(s):  
Spinal Cord ◽  
Spinal Pain ◽  
Pain Modulation ◽  
Painful Stimulus ◽  
Conditioned Pain Modulation ◽  
Pain Processing ◽  
Diffuse Noxious Inhibitory Controls ◽  
Inhibitory System ◽  
Reverse Translation ◽  
Human Counterpart

Abstract Descending controls link higher processing of noxious signals to modulation of spinal cord responses to their noxious inputs. It has become possible to study one key inhibitory system in animals and humans using one painful stimulus to attenuate another distant response and so eliciting diffuse noxious inhibitory controls (DNIC) or the human counterpart, conditioned pain modulation (CPM). Here, we discuss the neuronal pathways in both species, their pharmacology and examine changes in descending controls with a focus on osteoarthritis. We will also discuss the opposing descending facilitatory system. Strong parallels between DNIC and CPM emphasize the possibility of forward and reverse translation.

scholarly journals Projection Neuron Axon Collaterals in the Dorsal Horn: Placing a New Player in Spinal Cord Pain Processing

2020 ◽  
Vol 11 ◽  
Author(s):  
Tyler J. Browne ◽  
David I. Hughes ◽  
Christopher V. Dayas ◽  
Robert J. Callister ◽  
Brett A. Graham
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Pain ◽  
Spinal Cord Dorsal Horn ◽  
Axon Collateral ◽  
Pain Processing ◽  
Axon Collaterals ◽  
Output Neurons ◽  
Local Circuits ◽  
Collateral System

The pain experience depends on the relay of nociceptive signals from the spinal cord dorsal horn to higher brain centers. This function is ultimately achieved by the output of a small population of highly specialized neurons called projection neurons (PNs). Like output neurons in other central nervous system (CNS) regions, PNs are invested with a substantial axon collateral system that ramifies extensively within local circuits. These axon collaterals are widely distributed within and between spinal cord segments. Anatomical data on PN axon collaterals have existed since the time of Cajal, however, their function in spinal pain signaling remains unclear and is absent from current models of spinal pain processing. Despite these omissions, some insight on the potential role of PN axon collaterals can be drawn from axon collateral systems of principal or output neurons in other CNS regions, such as the hippocampus, amygdala, olfactory cortex, and ventral horn of the spinal cord. The connectivity and actions of axon collaterals in these systems have been well-defined and used to confirm crucial roles in memory, fear, olfaction, and movement control, respectively. We review this information here and propose a framework for characterizing PN axon collateral function in the dorsal horn. We highlight that experimental approaches traditionally used to delineate axon collateral function in other CNS regions are not easily applied to PNs because of their scarcity relative to spinal interneurons (INs), and the lack of cellular organization in the dorsal horn. Finally, we emphasize how the rapid development of techniques such as viral expression of optogenetic or chemogenetic probes can overcome these challenges and allow characterization of PN axon collateral function. Obtaining detailed information of this type is a necessary first step for incorporation of PN collateral system function into models of spinal sensory processing.

Conditioned pain modulation decreases dorsal horn BOLD signal in the human spinal cord

2013 ◽  
Vol 14 (4) ◽  
pp. S46
Author(s):  
P. Nash ◽  
B. Reyes ◽  
E. Hubbard ◽  
S. Mackey
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Bold Signal ◽  
Human Spinal Cord

Moving From an Averaged to Specific View of Spinal Cord Pain Processing Circuits

2007 ◽  
Vol 98 (3) ◽  
pp. 1057-1063 ◽  
Author(s):  
B. A. Graham ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Spinal Pain ◽  
Pain Processing ◽  
In Vivo Animal Models ◽  
Processing Mechanisms ◽  
Made In

Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This same notion also underlies treatments for certain chronic pain states. Basic scientists are now beginning to identify a number of potential molecular targets for spinal cord–based pain therapies with a focus on ion channels and receptors that can alter neuronal excitability. The current challenge in pain research is to identify which are the most promising targets and how their manipulation alters pain processing. In this review, we propose that our understanding of spinal pain processing mechanisms and translation of these discoveries into pain therapies could be improved by 1) better appreciating and understanding neuronal heterogeneity in the SDH; 2) establishing connectivity patterns among SDH neuron types; and 3) testing and extending findings made in vitro to intact (in vivo) animal models. As this information becomes available, it will be possible to determine the precise distribution of potential therapeutic targets on various SDH neuron types within specific circuits known to be functionally important in spinal pain processing.

scholarly journals An Investigation of Descending Pain Modulation in Women With Provoked Vestibulodynia (PVD): Alterations of Spinal Cord and Brainstem Connectivity

2021 ◽  
Vol 2 ◽  
Author(s):  
Lindsey R. Yessick ◽  
Caroline F. Pukall ◽  
Gabriela Ioachim ◽  
Susan M. Chamberlain ◽  
Patrick W. Stroman
Keyword(s):  
Spinal Cord ◽  
Functional Connectivity ◽  
Structural Equation ◽  
Brain Regions ◽  
Pain Modulation ◽  
Equation Modeling ◽  
Control Group ◽  
Pain Processing ◽  
Provoked Vestibulodynia ◽  
Fmri Session

The most common subtype of vulvodynia (idiopathic chronic vulvar pain) is provoked vestibulodynia (PVD). Previous imaging studies have shown that women with vulvodynia exhibit increased neural activity in pain-related brain regions (e.g., the secondary somatosensory cortex, insula, dorsal midcingulate, posterior cingulate, and thalamus). However, despite the recognized role of the spinal cord/brainstem in pain modulation, no previous neuroimaging studies of vulvodynia have examined the spinal cord/brainstem. Sixteen women with PVD and sixteen matched Control women underwent a spinal cord/brainstem functional magnetic resonance imaging (fMRI) session consisting of five runs with no painful thermal stimuli (No Pain), interleaved randomly with five runs with calibrated, moderately painful heat stimulation (Pain). Functional connectivity was also assessed in periods before, during, and after, pain stimulation to investigate dynamic variations in pain processing throughout the stimulation paradigm. Functional connectivity in the brainstem and spinal cord for each group was examined using structural equation modeling (SEM) for both Pain and No Pain conditions. Significant connectivity differences during stimulation were identified between PVD and Control groups within pain modulatory regions. Comparisons of Pain and No Pain conditions identified a larger number of connections in the Control group than in the PVD group, both before and during stimulation. The results suggest that women with PVD exhibit altered pain processing and indicate an insufficient response of the pain modulation system. This study is the first to examine the spinal cord/brainstem functional connectivity in women with PVD, and it demonstrates altered connectivity related to pain modulation in the spinal cord/brainstem.

scholarly journals Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

2020 ◽  
Vol 34 (11) ◽  
pp. 997-1008
Author(s):  
Martin Gagné ◽  
Isabelle Côté ◽  
Mélanie Boulet ◽  
Catherine R. Jutzeler ◽  
John L. K. Kramer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Heat Pain ◽  
Heat Pain Threshold ◽  
Cord Injury ◽  
Prospective Longitudinal ◽  
Over Time

Background Neuropathic pain is a major problem following spinal cord injury (SCI). Central mechanisms involved in the modulation of nociceptive signals have been shown to be altered at the chronic stage, and it has been hypothesized that they might play a role in the development of chronic pain. Objective This prospective longitudinal study aimed to describe the evolution of pain modulation mechanisms over time after SCI, and to explore the relationships with the presence of clinical (neuropathic and musculoskeletal) pain. Methods Patients with an SCI were assessed on admission (n = 35; average of 38 days postinjury) and discharge (n = 25; average of 131 days postinjury) using the International Spinal Cord Injury Pain Basic Data Set. Conditioned pain modulation was assessed using the cold pressor test (10 °C; 120 s) as the conditioning stimulus and tonic heat pain, applied above the level of injury, as the test stimulus (120 s). Heat pain threshold was also assessed. Results A marked decrease in the efficacy of conditioned pain modulation was observed over time, with 30.2% of inhibition at admission and only 12.9% at discharge on average ( P = .010). This decrease was observed only in patients already suffering from neuropathic pain at admission and was not explained by a general increase in sensitivity to thermal nociceptive stimuli. Conclusion These results suggest that the presence of neuropathic pain leads to a decrease in conditioned pain modulation over time, rather than supporting the hypothesis that inefficient conditioned pain modulation mechanisms are leading to the development of neuropathic pain.

Local hyperalgesia, normal endogenous modulation with pain report beyond its origin: a pilot study prompting further exploration into plantar fasciopathy

2020 ◽  
Vol 20 (2) ◽  
pp. 375-385
Author(s):  
Henrik Riel ◽  
Melanie L. Plinsinga ◽  
Rebecca Mellor ◽  
Shellie A. Boudreau ◽  
Viana Vuvan ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Pain Threshold ◽  
Pressure Pain Threshold ◽  
Plantar Fascia ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Processing ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Plantar Fasciopathy

AbstractBackground and aimsPersistent tendinopathies were previously considered solely as peripheral conditions affecting the local tendinous tissue until quantitative sensory testing identified involvement of altered pain processing. In similar fashion, pain in patients with persistent plantar fasciopathy may also involve more than local tissue. The aim of this pilot study was to investigate potential differences in conditioned pain modulation and pressure and thermal pain thresholds, between individuals with PF and healthy pain-free controls, as a precursor to a larger-scale study.MethodsWe assessed 16 individuals with plantar fasciopathy and 11 pain-free controls. Plantar fasciopathy diagnosis was: palpation pain of the medial calcaneal tubercle or the proximal plantar fascia, duration ≥3 months, pain intensity ≥2/10, and ultrasound-measured plantar fascia thickness ≥4 mm. Quantitative sensory tests were performed locally at the plantar heel and remotely on the ipsilateral elbow. Assessments included pain thresholds for pressure, heat and cold, and conditioned pain modulation measured as change in local resting pressure pain threshold with cold water hand immersion. Participants rated pain intensity at pain threshold. Additionally, the area and distribution of plantar fasciopathy pain was drawn on a digital body chart of the lower limbs. Descriptive analyses were performed and between-group differences/effects expressed as standardised mean differences (d).ResultsThere was no conditioned pain modulation difference between participants with plantar fasciopathy and controls (d = 0.1). Largest effects were on local pressure pain threshold and reported pain intensity on pressure pain threshold (d > 1.8) followed by pain intensity for heat and cold pain thresholds (d = 0.3–1.5). According to the digital body chart, pain area extended beyond the plantar heel.ConclusionsThe unlikelihood of a difference in conditioned pain modulation yet a pain area extending beyond the plantar heel provide a basis for exploring altered pain processing in a larger-scale study.ImplicationsThis was the first study to investigate the presence of altered pain processing in individuals with plantar fasciopathy using a conditioned pain modulation paradigm and thermal pain thresholds. We found no indication of an altered pain processing based on these measures, however, patients rated pain higher on thresholds compared to controls which may be important to clinical practice and warrants further exploration in the future.

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control

Cephalalgia ◽  
2009 ◽  
Vol 30 (3) ◽  
pp. 272-284 ◽  
Author(s):  
A Perrotta ◽  
M Serrao ◽  
G Sandrini ◽  
R Burstein ◽  
G Sances ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Pain Processing ◽  
Diffuse Noxious Inhibitory Controls ◽  
Spinal Level ◽  
Pressor Test ◽  
Withdrawal Treatment

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.

scholarly journals Effectiveness of Unihemispheric Concurrent Dual-Site Stimulation over M1 and Dorsolateral Prefrontal Cortex Stimulation on Pain Processing: A Triple Blind Cross-Over Control Trial

2021 ◽  
Vol 11 (2) ◽  
pp. 188
Author(s):  
Francisco Gurdiel-Álvarez ◽  
Yeray González-Zamorano ◽  
Sergio Lerma Lara ◽  
Julio Gómez-Soriano ◽  
Julian Taylor ◽  
...  
Keyword(s):  
Dorsolateral Prefrontal Cortex ◽  
Pain Modulation ◽  
Pain Tolerance ◽  
Conditioned Pain Modulation ◽  
Pain Processing ◽  
Pressure Pain ◽  
Dorsolateral Prefrontal ◽  
Before And After ◽  
Cold Hyperalgesia ◽  
Dual Site

Background: Transcranial direct current stimulation (tDCS) of the motor cortex (M1) produces short-term inhibition of pain. Unihemispheric concurrent dual-site tDCS (UHCDS-tDCS) over the M1 and dorsolateral prefrontal cortex (DLPFC) has greater effects on cortical excitability than when applied alone, although its effect on pain is unknown. The aim of this study was to test if anodal UHCDS-tDCS over the M1 and DLPFC in healthy participants could potentiate conditioned pain modulation (CPM) and diminish pain temporal summation (TS). Methods: Thirty participants were randomized to receive a sequence of UHCDS-tDCS, M1-tDCS and sham-tDCS. A 20 min 0.1 mA/cm2 anodal or sham-tDCS intervention was applied to each participant during three test sessions, according to a triple-blind cross-over trial design. For the assessment of pain processing before and after tDCS intervention, the following tests were performed: tourniquet conditioned pain modulation (CPM), pressure pain temporal summation (TS), pressure pain thresholds (PPTs), pressure pain tolerance, mechanosensitivity and cold hyperalgesia. Motor function before and after tDCS intervention was assessed with a dynamometer to measure maximal isometric grip strength. Results: No statistically significant differences were found between groups for CPM, pressure pain TS, PPT, pressure pain tolerance, neural mechanosensitivity, cold hyperalgesia or grip strength (p > 0.05). Conclusions: Neither UHCDS-tDCS nor M1-tDCS facilitated CPM or inhibited TS in healthy subjects following one intervention session.

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