Immune and glial cell factors as pain mediators and modulators

McMahon, Stephen B.; Cafferty, William B. J.; Marchand, Fabien

doi:10.1016/j.expneurol.2004.11.001

Cited by 396 publications

(322 citation statements)

References 170 publications

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“…Recent research has highlighted the importance of glial cells in relation to pain (Inoue and Tsuda, 2009;McMahon et al, 2005;Miller et al, 2009), and in processes such as synaptic plasticity, important for learning and memory (Bains and Oliet, 2007). Furthermore, activated glial cells can release a variety of cytokines and neurotrophic factors which also modulate neural processes involved in pain and cognition (Covey et al, 2000;Ren and Dubner, 2008;Tanaka et al, 2006).…”

Section: Glial Cells and Cytokines In Pain And Cognitionmentioning

confidence: 99%

The effect of pain on cognitive function: A review of clinical and preclinical research

Moriarty

McGuire

Finn

2011

Progress in Neurobiology

872

710

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Cognitive impairment is commonly associated with the pain experience. This impairment represents a major obstacle to daily activities and rehabilitation, especially in the chronic pain population. Here we review clinical and preclinical studies that have investigated pain-related alterations in cognition. These include impaired attentional, executive and general cognitive functioning. We describe the anatomical, neurochemical and molecular substrates common to both cognitive processing and supraspinal pain processing, and present the evidence for their involvement in pain-related cognitive impairment. We also examine the added complexity of cognitive impairment caused by analgesic medications and how this can further impact on morbidity in chronic pain patients. The need for a better understanding of the mechanisms of both pain-induced and treatment-related cognitive impairment is highlighted. Further research in this area will aid our understanding of patient symptoms and their underlying pathophysiology, ultimately leading to increased provision of guided therapy.

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Section: Glial Cells and Cytokines In Pain And Cognitionmentioning

confidence: 99%

The effect of pain on cognitive function: A review of clinical and preclinical research

Moriarty

McGuire

Finn

2011

Progress in Neurobiology

872

710

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“…Glia act to dynamically regulate neuronal synaptic communication (Haydon, 2001), and can lead to pathological pain via the release of a variety of neurotransmitters, neuromodulators (McMahon et al, 2005), proinflammatory cytokines and chemokines (Rostene et al, 2007). Astrocytes are closely associated with neuronal somas, dendrites, and pre-and postsynaptic sites, as well as with other glia (microglia), and their functions are now understood to include active, integrative roles during synaptic transmission (Fellin et al, 2006, Haydon, 2001.…”

Section: Glial Modulation Of Neuronal Activitymentioning

confidence: 99%

Glia in pathological pain: A role for fractalkine

Milligan

Sloane

Watkins

2008

Journal of Neuroimmunology

104

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Microglia and/or astrocytes play a significant role in the creation and maintenance of exaggerated pain states with inflammatory and/or neuropathic etiologies. The chemokine, fractalkine, has several functions, including the newly recognized role of mediating neuropathic pain conditions. Although constitutively expressed and released during inflammation, increased release of fractalkine binds to and activates microglia glia leading to pathological pain. We review the critical role of fractalkine in neuron-to-glial communication after peripheral nerve injury and inflammation and explore anti-inflammatory cytokines like interleukin-10 as a novel and effective approach for clinical pain control. KeywordsNeuropathic pain; spinal cord; microglia; astrocytes; interleukin-10; gene therapy Previously Understood Views of PainTraditionally, our understanding about neuronal signaling for pain transmission from the body to the central nervous system (CNS) occurs as a series of relay signals that are eventually processed in the brain. These relay signals are thought to serve protective and adaptive roles, with the first synaptic relay, between the first order (sensory) neuron and the second order neuron in the dorsal horn of the spinal cord. Neurons that receive and respond to pain information are primarily located in anatomically discrete regions of the spinal cord, that is, laminae I, II and V of the spinal cord dorsal horns. From the spinal cord dorsal horn, pain projection neurons relay their information to higher pain centers, such as to the brainstem and various relevant pain areas in the brain. Interestingly, the dorsal horn of the spinal cord can strongly modulate pain signaling (Millan, 1999). Although the neuronal functioning of these pain pathways has been examined for decades, the induction and maintenance of non-adaptive, pathological pain is poorly understood. However, since the early 1990's, there has been mounting evidence that glial cells (both astrocytes and microglia), in addition to neurons, also play a critical role in pain modulation (DeLeo et al., 2007).

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“…The question can be addressed by distinguishing signals generated when axon damage interrupts central (retrograde) transport of constitutive molecules (negative injury signals) versus ones that are newly introduced, activated, or modified by axon injury (positive injury signals) (Ambron and Walters, 1996;Perlson et al, 2004;McMahon et al, 2005). Both negative and positive injury signals have been shown to initiate synaptic change (Lessmann, 1998;Mendell et al, 1999;Woolf and Costigan, 1999;Mendell and Arvanian, 2002;Kohno et al, 2003;Du and Poo, 2004;Sung et al, 2004;McMahon et al, 2005). For IA-MN synapses, deprivation of muscle-derived neurotrophin NT3 may contribute to the decline in EPSP amplitude that occurs Ͼ1 week after nerve section (Mendell et al, 2001).…”

Section: Signals Initiating Synaptic Enhancementmentioning

confidence: 99%

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

Bichler¹,

Nakanishi²,

Wang³

et al. 2007

J. Neurosci.

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Peripheral nerve crush initiates a robust increase in transmission strength at spinal synapses made by axotomized group IA primary sensory neurons. To study the injury signal that initiates synaptic enhancement in vivo, we designed experiments to manipulate the enlargement of EPSPs produced in spinal motoneurons (MNs) by IA afferents 3 d after nerve crush in anesthetized adult rats. If nerve crush initiates IA EPSP enlargement as proposed by reducing impulse-evoked transmission in crushed IA afferents, then restoring synaptic activity should eliminate enlargement. Daily electrical stimulation of the nerve proximal to the crush site did, in fact, eliminate enlargement but was, surprisingly, just as effective when the action potentials evoked in crushed afferents were prevented from propagating into the spinal cord. Consistent with its independence from altered synaptic activity, we found that IA EPSP enlargement was also eliminated by colchicine blockade of axon transport in the crushed nerve. Together with the observation that colchicine treatment of intact nerves had no short-term effect on IA EPSPs, we conclude that enhancement of IA-MN transmission is initiated by some yet to be identified positive injury signal generated independent of altered synaptic activity. The results establish a new set of criteria that constrain candidate signaling molecules in vivo to ones that develop quickly at the peripheral injury site, move centrally by axon transport, and initiate enhanced transmission at the central synapses of crushed primary sensory afferents through a mechanism that can be modulated by action potential activity restricted to the axons of crushed afferents.

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Immune and glial cell factors as pain mediators and modulators

Cited by 396 publications

References 170 publications

The effect of pain on cognitive function: A review of clinical and preclinical research

The effect of pain on cognitive function: A review of clinical and preclinical research

Glia in pathological pain: A role for fractalkine

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

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