Early Afferent Activity from the Facet Joint After Painful Trauma to Its Capsule Potentiates Neuronal Excitability and Glutamate Signaling in the Spinal Cord

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2014 Jul 1

PMID 24978827

Citations 15

Authors

Nathan D Crosby

Taylor M Gilliland

Beth A Winkelstein

Affiliations

Soon will be listed here.

Abstract

Cervical facet joint injury induces persistent pain and central sensitization. Preventing the peripheral neuronal signals that initiate sensitization attenuates neuropathic pain. Yet, there is no clear relationship among facet joint afferent activity, development of central sensitization, and pain, which may be hindering effective treatments for this pain syndrome. This study investigates how afferent activity from the injured cervical facet joint affects induction of behavioral sensitivity and central sensitization. Intra-articular bupivacaine was administered to transiently suppress afferent activity immediately or 4 days after facet injury. Mechanical hyperalgesia was monitored after injury, and spinal neuronal hyperexcitability and spinal expression of proteins that promote neuronal excitability were measured on day 7. Facet injury with saline vehicle treatment induced significant mechanical hyperalgesia (P<.027), dorsal horn neuronal hyperexcitability (P<.026), upregulation of pERK1/2, pNR1, mGluR5, GLAST, and GFAP, and downregulation of GLT1 (P<.032). However, intra-articular bupivacaine immediately after injury significantly attenuated hyperalgesia (P<.0001), neuronal hyperexcitability (P<.004), and dysregulation of excitatory signaling proteins (P<.049). In contrast, intra-articular bupivacaine at day 4 had no effect on these outcomes. Silencing afferent activity during the development of neuronal hyperexcitability (4 hours, 8 hours, 1 day) attenuated hyperalgesia and neuronal hyperexcitability (P<.045) only for the treatment given 4 hours after injury. This study suggests that early afferent activity from the injured facet induces development of spinal sensitization via spinal excitatory glutamatergic signaling. Peripheral intervention blocking afferent activity is effective only over a short period of time early after injury and before spinal modifications develop, and is independent of modulating spinal glial activation.

Citing Articles

Fabry disease Schwann cells release p11 to induce sensory neuron hyperactivity.

Waltz T, Chao D, Prodoehl E, Enders J, Ehlers V, Dharanikota B JCI Insight. 2024; 9(8).

PMID: 38646936 PMC: 11141882. DOI: 10.1172/jci.insight.172869.

Annulus Fibrosus Injury Induces Acute Neuroinflammation and Chronic Glial Response in Dorsal Root Ganglion and Spinal Cord-An In Vivo Rat Discogenic Pain Model.

Lai A, Iliff D, Zaheer K, Gansau J, Laudier D, Zachariou V Int J Mol Sci. 2024; 25(3).

PMID: 38339040 PMC: 10855200. DOI: 10.3390/ijms25031762.

Inhibiting spinal secretory phospholipase A after painful nerve root injury attenuates established pain and spinal neuronal hyperexcitability by altering spinal glutamatergic signaling.

Kartha S, Ghimire P, Winkelstein B Mol Pain. 2021; 17:17448069211066221.

PMID: 34919471 PMC: 8721705. DOI: 10.1177/17448069211066221.

Repeated High Rate Facet Capsular Stretch at Strains That are Below the Pain Threshold Induces Pain and Spinal Inflammation With Decreased Ligament Strength in the Rat.

Kartha S, Bulka B, Stiansen N, Troche H, Winkelstein B J Biomech Eng. 2018; 140(8).

PMID: 30003250 PMC: 6056195. DOI: 10.1115/1.4040023.

Multiscale mechanics of the cervical facet capsular ligament, with particular emphasis on anomalous fiber realignment prior to tissue failure.

Zhang S, Zarei V, Winkelstein B, Barocas V Biomech Model Mechanobiol. 2017; 17(1):133-145.

PMID: 28821971 PMC: 5809183. DOI: 10.1007/s10237-017-0949-8.

References

Lu Y, Chen C, Kallakuri S, Patwardhan A, Cavanaugh J . Neural response of cervical facet joint capsule to stretch: a study of whiplash pain mechanism. Stapp Car Crash J. 2006; 49:49-65. DOI: 10.4271/2005-22-0003. View

Winkelstein B, Santos D . An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension. Spine (Phila Pa 1976). 2008; 33(8):856-62. DOI: 10.1097/BRS.0b013e31816b4710. View

Benveniste E . Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol. 1992; 263(1 Pt 1):C1-16. DOI: 10.1152/ajpcell.1992.263.1.C1. View

Roy D, Fleury J, FONTAINE S, Dussault R . Clinical evaluation of cervical facet joint infiltration. Can Assoc Radiol J. 1988; 39(2):118-20. View

Hogg-Johnson S, van der Velde G, Carroll L, Holm L, Cassidy J, Guzman J . The burden and determinants of neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976). 2008; 33(4 Suppl):S39-51. DOI: 10.1097/BRS.0b013e31816454c8. View

Kras J, Tanaka K, Gilliland T, Winkelstein B . An anatomical and immunohistochemical characterization of afferents innervating the C6-C7 facet joint after painful joint loading in the rat. Spine (Phila Pa 1976). 2013; 38(6):E325-31. PMC: 3600108. DOI: 10.1097/BRS.0b013e318285b5bb. View

Lee K, Winkelstein B . Joint distraction magnitude is associated with different behavioral outcomes and substance P levels for cervical facet joint loading in the rat. J Pain. 2009; 10(4):436-45. DOI: 10.1016/j.jpain.2008.11.009. View

Kiyatkin A, Aksamitiene E . Multistrip western blotting to increase quantitative data output. Methods Mol Biol. 2009; 536:149-61. PMC: 2923389. DOI: 10.1007/978-1-59745-542-8_17. View

McLain R . Mechanoreceptor endings in human cervical facet joints. Spine (Phila Pa 1976). 1994; 19(5):495-501. DOI: 10.1097/00007632-199403000-00001. View

10.

Lee K, Davis M, Mejilla R, Winkelstein B . In vivo cervical facet capsule distraction: mechanical implications for whiplash and neck pain. Stapp Car Crash J. 2007; 48:373-95. DOI: 10.4271/2004-22-0016. View

11.

Araujo M, Sinnott C, Strichartz G . Multiple phases of relief from experimental mechanical allodynia by systemic lidocaine: responses to early and late infusions. Pain. 2003; 103(1-2):21-9. DOI: 10.1016/s0304-3959(02)00350-0. View

12.

Kras J, Dong L, Winkelstein B . Increased interleukin-1α and prostaglandin E2 expression in the spinal cord at 1 day after painful facet joint injury: evidence of early spinal inflammation. Spine (Phila Pa 1976). 2013; 39(3):207-12. PMC: 3946680. DOI: 10.1097/BRS.0000000000000107. View

13.

Yamashita T, Cavanaugh J, Getchell T, King A . Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am. 1990; 72(6):865-70. View

14.

Barnsley L, Bogduk N . Medial branch blocks are specific for the diagnosis of cervical zygapophyseal joint pain. Reg Anesth. 1993; 18(6):343-50. View

15.

Yang F, Whang J, Derry W, Vardeh D, Scholz J . Analgesic treatment with pregabalin does not prevent persistent pain after peripheral nerve injury in the rat. Pain. 2013; 155(2):356-366. DOI: 10.1016/j.pain.2013.10.024. View

16.

Latremoliere A, Woolf C . Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009; 10(9):895-926. PMC: 2750819. DOI: 10.1016/j.jpain.2009.06.012. View

17.

Lee K, Davis M, Winkelstein B . Capsular ligament involvement in the development of mechanical hyperalgesia after facet joint loading: behavioral and inflammatory outcomes in a rodent model of pain. J Neurotrauma. 2008; 25(11):1383-93. DOI: 10.1089/neu.2008.0700. View

18.

Liu C, Wall P, Ben-Dor E, Michaelis M, Amir R, Devor M . Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. Pain. 2000; 85(3):503-521. DOI: 10.1016/S0304-3959(00)00251-7. View

19.

WALL P, Woolf C . The brief and the prolonged facilitatory effects of unmyelinated afferent input on the rat spinal cord are independently influenced by peripheral nerve section. Neuroscience. 1986; 17(4):1199-205. DOI: 10.1016/0306-4522(86)90087-4. View

20.

Pekny M, Nilsson M . Astrocyte activation and reactive gliosis. Glia. 2005; 50(4):427-434. DOI: 10.1002/glia.20207. View