20 Workshop Summary: ECTOPIC DISCHARGES IN C-NOCICEPTORS AS A CAUSE OF NEUROPATHIC PAIN

2007 ◽  
Vol 11 (S1) ◽  
pp. S8-S9
Author(s):  
J. Serra
Keyword(s):  
Neuropathic Pain ◽  
Workshop Summary ◽  
Ectopic Discharges

Pain neurophysiology

2013 ◽  
Author(s):  
Hans-Georg Schaible ◽  
Rainer H. Straub
Keyword(s):  
Neuropathic Pain ◽  
Central Sensitization ◽  
Cell Activation ◽  
Warning Signal ◽  
Nociceptive Pain ◽  
Neural Function ◽  
Peripheral Sensitization ◽  
Nerve Fibres ◽  
Glial Cell Activation ◽  
Ectopic Discharges

Physiological pain is evoked by intense (noxious) stimuli acting on healthy tissue functioning as a warning signal to avoid damage of the tissue. In contrast, pathophysiological pain is present in the course of disease, and it is often elicited by low-intensity stimulation or occurs even as resting pain. Causes of pathophysiological pain are either inflammation or injury causing pathophysiological nociceptive pain or damage to nerve cells evoking neuropathic pain. The major peripheral neuronal mechanism of pathophysiological nociceptive pain is the sensitization of peripheral nociceptors for mechanical, thermal and chemical stimuli; the major peripheral mechanism of neuropathic pain is the generation of ectopic discharges in injured nerve fibres. These phenomena are created by changes of ion channels in the neurons, e.g. by the influence of inflammatory mediators or growth factors. Both peripheral sensitization and ectopic discharges can evoke the development of hyperexcitability of central nociceptive pathways, called central sensitization, which amplifies the nociceptive processing. Central sensitization is caused by changes of the synaptic processing, in which glial cell activation also plays an important role. Endogenous inhibitory neuronal systems may reduce pain but some types of pain are characterized by the loss of inhibitory neural function. In addition to their role in pain generation, nociceptive afferents and the spinal cord can further enhance the inflammatory process by the release of neuropeptides into the innervated tissue and by activation of sympathetic efferent fibres. However, in inflamed tissue the innervation is remodelled by repellent factors, in particular with a loss of sympathetic nerve fibres.

Receptor Subtype Mediating the Adrenergic Sensitivity of Pain Behavior and Ectopic Discharges in Neuropathic Lewis Rats

1999 ◽  
Vol 81 (5) ◽  
pp. 2226-2233 ◽  
Author(s):  
Doo Hyun Lee ◽  
Xianzeng Liu ◽  
Hyun Taek Kim ◽  
Kyungsoon Chung ◽  
Jin Mo Chung
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Pain Behavior ◽  
Receptor Subtype ◽  
Systemic Injection ◽  
Lewis Rats ◽  
Ectopic Discharges

Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of α-adrenergic receptor (α-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general α-AR blocker. We examined the effects of specific α1- and α2-AR blockers on 1) behavioral signs of mechanical allodynia, 2) ectopic discharges recorded in the in vivo condition, and 3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed α1- and α2-AR antagonist) or terazosin (TRZ, an α1-AR antagonist) but not by various α2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the α1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving α1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the α1 subtype of AR.

scholarly journals Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yu-Juan Qu ◽  
Xiao Zhang ◽  
Zhen-Zhen Fan ◽  
Juan Huai ◽  
Yong-Bo Teng ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Mapk Pathway ◽  
Intrathecal Injection ◽  
Ruthenium Red ◽  
Protein Expressions ◽  
Intermediary Role ◽  
Ectopic Discharges

The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4) and anisomycin (an agonist of p38), but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4) and SB203580 (an inhibitor of p38). The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

Characteristics of ectopic discharges in a rat neuropathic pain model

Pain ◽  
2000 ◽  
Vol 84 (2) ◽  
pp. 253-261 ◽  
Author(s):  
Hee Chul Han ◽  
Doo Hyun Lee ◽  
Jin Mo Chung
Keyword(s):  
Neuropathic Pain ◽  
Pain Model ◽  
Neuropathic Pain Model ◽  
Ectopic Discharges

Development of Neuropathic Pain in the Rat Spared Nerve Injury Model Is Not Prevented by a Peripheral Nerve Block

2003 ◽  
Vol 99 (6) ◽  
pp. 1402-1408 ◽  
Author(s):  
Marc R. Suter ◽  
Michael Papaloïzos ◽  
Charles B. Berde ◽  
Clifford J. Woolf ◽  
Nicolas Gilliard ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Conduction Block ◽  
Radiant Heat ◽  
Detectable Effect ◽  
Spared Nerve Injury ◽  
Injury Model ◽  
The Central Nervous System ◽  
Ectopic Discharges

Background The mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. One hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. The aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model. Methods Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. After sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. Development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n = 12) and in controls (n = 11). Results Bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. Once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups. Conclusions Peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. It is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.

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