Endogenous Facilitation: From Molecular Mechanisms to Persistent Pain

Robinson, Daniel M.; Calejesan, Amelita A.; Feng, Wei; Gebhart, G. F.; Zhuo, Min

doi:10.2174/1567202043480189

Cited by 24 publications

(17 citation statements)

References 43 publications

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“…GABA(c-aminobutyric acid)-and glycinergic spinal circuits play important role in the development of inflammatory pain (Robinson et al, 2004). It was suggested that spinal inhibition prevents a significant portion of deep dorsal horn neurons from becoming Fig.…”

Section: Discussionmentioning

confidence: 99%

Acute muscle inflammation enhances the monosynaptic reflexes and c‐fos expression in the feline spinal cord

Schomburg¹,

Steffens²,

Maznychenko

et al. 2007

European Journal of Pain

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The aim of this research was to study the changes of the motor reflex activity (monosynaptic reflex (MSR) of the flexor and extensor muscles) and Fos immunoreactivity in lumbo-sacral spinal cord after acute induced myositis of m. gastrocnemius-soleus (GS). The experiments were carried out on ischaemic decerebrated, spinalized in C1 cats. After infiltration of the GS muscle with carrageenan (2%) MSRs of flexors and extensors showed a significant increase in amplitude +127+/-24.5% and +155+/-28.5%, respectively, p<0.05. The exposed effect was initiated within 30 min and achieved a maximum 2.8h after the intramuscular injections of carrageenan. After analysis of dynamics of the MSRs, animals were perfused and c-fos expression in the spinal segments L6-S1 was evaluated. In comparison to sham-operated animals, the number of Fos-immunoreactive (Fos-ir) cells was noticeably increased in the lumbar cord of cats with carrageenan-induced myositis. The labeled cells were concentrated in the ipsilateral laminae I/II, neck of the dorsal horn (V/VI) and intermediate zone (VII), however, clear predominance of their concentration was found in the deep laminae. The effect of muscle inflammation was also expressed as a significant decline in the number of NADPH-d-reactive cells (p<0.05) in ipsilateral laminae I/II of L6/L7. The results show that the input from acutely inflamed muscles may induce an increase of the reflex responsiveness of flexors and extensors which is not mediated via the gamma-spindle-loop and which coincides with a significant increase in c-fos expression in the deep laminae of the lumbar spinal cord.

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Section: Discussionmentioning

confidence: 99%

Acute muscle inflammation enhances the monosynaptic reflexes and c‐fos expression in the feline spinal cord

Schomburg¹,

Steffens²,

Maznychenko

et al. 2007

European Journal of Pain

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“…However, compelling evidence demonstrates that descending control is bi‐directional via inhibitory and facilitatory systems. In addition to activating descending inhibitory pathways, peripheral nociceptive afferents are also capable of activating descending facilitatory pathways, particularly in pathological conditions (Robinson et al ., 2004). Sustained activation of descending facilitation increases excitability of spinal nociceptive neurons and in turn evokes neuroplasticity of some supraspinal structures including the ACC and RVM (Wei et al ., 1999; Porreca et al ., 2002; Robinson et al ., 2002), suggesting that sustained activation of descending facilitation could underlie some states of inflammatory and neuropathic pain (Porreca et al ., 2002).…”

Section: Discussionmentioning

confidence: 99%

Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus

Zhang

Zhao

2005

Eur J of Neuroscience

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Supraspinal centres biphasically modulate spinal nociceptive transmission, including descending inhibition and facilitation. Recent studies have revealed that descending facilitatory modulation is a key mechanism underlying induction and maintenance of neuropathic and inflammatory pain. The anterior cingulate cortex (ACC) is not only involved in the transmission of pain sensation but also plays a role in processing pain-related emotion. The ACC also widely connects with relevant regions of the descending modulation system. Here we used electrophysiological and behavioural techniques to study the possible pathways behind the modulation of spinal nociceptive transmission from the ACC. C-fibre-evoked field potentials in the spinal dorsal horn were produced by electrical stimulation of the sciatic nerve at an intensity high enough to excite C fibres, and paw withdrawal latencies (PWLs) to noxious heating were recorded. The results showed that high-frequency tetanic electrical stimulation of the ACC both unilaterally enhanced the C-fibre-evoked field potentials in the spinal dorsal horn and bilaterally shortened PWLs, indicating a facilitation of spinal nociception. A similar effect was observed after microinjection of N-methyl-d-aspartic acid (NMDA; 10 nm, 1 microL) or homocysteic acid (HCA; 0.1 m, 1 microL) into the ACC. When the dorsal reticular nucleus (DRt) was electrolytically lesioned, ACC-induced facilitation of spinal nociception was blocked. These results imply that: (i) activation of the ACC may facilitate spinal nociception; (ii) NMDA receptors in the ACC may be involved in descending facilitation; and (iii) the DRt plays a crucial role in mediating ACC-induced facilitation of spinal nociception.

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“…Understanding the specific cascade of changes that generate and maintain central sensitisation would significantly expand our ability to design targeted therapies to treat the central sensitisation that occurs following many types of skeletal pain. These neurochemical and electrophysiological changes appear to occur in the ascending and descending pain pathways of the spinal cord, brainstem, thalamus and cerebral cortex, and all of these changes may contribute to the amplified perception of skeletal pain (Basbaum & Fields, 1978;Gebhart, 2004;Robinson et al, 2004;Hunt, 2009;Latremoliere & Woolf, 2009;Woolf, 2011;Yoshida et al, 2013).…”

Section: Central Sensitisation and Skeletal Painmentioning

confidence: 99%

The neurobiology of skeletal pain

Mantyh

2014

Eur J of Neuroscience

153

158

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Disorders of the skeleton are one of the most common causes of chronic pain and long-term physical disability in the world. Chronic skeletal pain is caused by a remarkably diverse group of conditions including trauma-induced fracture, osteoarthritis, osteoporosis, low back pain, orthopedic procedures, celiac disease, sickle cell disease and bone cancer. While these disorders are diverse, what they share in common is that when chronic skeletal pain occurs in these disorders, there are currently few therapies that can fully control the pain without significant unwanted side effects. In this review we focus on recent advances in our knowledge concerning the unique population of primary afferent sensory nerve fibers that innervate the skeleton, the nociceptive and neuropathic mechanisms that are involved in driving skeletal pain, and the neurochemical and structural changes that can occur in sensory and sympathetic nerve fibers and the CNS in chronic skeletal pain. We also discuss therapies targeting nerve growth factor or sclerostin for treating skeletal pain. These therapies have provided unique insight into the factors that drive skeletal pain and the structural decline that occurs in the aging skeleton. We conclude by discussing how these advances have changed our understanding and potentially the therapeutic options for treating and/or preventing chronic pain in the injured, diseased and aged skeleton. GRAPHICAL ABSTRACT: Skeletal pain is common and frequently difficult to fully control. Recent data suggests that the skeleton is innervated by a restricted set of nociceptors and that many skeletal pains have both a nociceptive and a neuropathic component. Significant progress has been made in defining the mechanisms that drive skeletal pain and the factors that control skeletal remodeling. These insights have the potential to fundamentally transform our understanding and ability to prevent and/or treat skeletal pain due to injury, disease, and aging.

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Endogenous Facilitation: From Molecular Mechanisms to Persistent Pain

Cited by 24 publications

References 43 publications

Acute muscle inflammation enhances the monosynaptic reflexes and c‐fos expression in the feline spinal cord

Acute muscle inflammation enhances the monosynaptic reflexes and c‐fos expression in the feline spinal cord

Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus

The neurobiology of skeletal pain

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