Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia

1. Peripheral nerve injury sometimes leads to the development of neuropathic pain. One of the symptoms of such neuropathic pain is mechanical allodynia, pain in response to normally innocuous mechanical stimuli. We hypothesized that sympathetically driven dysfunction of cutaneous mechanoreceptors is responsible for signaling mechanical allodynia. The present study was undertaken to identify the types of sensory receptors that potentially mediate mechanical allodynia, with the use of a rat neuropathic pain model we have developed. 2. One week to 10 days after tight ligations of the L5 and L6 spinal nerves on one side, the rats fully developed behavioral signs of mechanical allodynia on the affected hindlimb. Various cutaneous mechanoreceptors originating from the neuropathic foot were examined by single-fiber recordings from the L4 dorsal root. 3. Although no particular abnormalities were found in other types of cutaneous mechanoreceptors, an unusual type of mechanoreceptor was found to be innervating the neuropathic foot. The response characteristics of this type of receptor resemble those of rapidly adapting mechanoreceptors (RAs), but with low and irregular static discharges during a maintained mechanical stimulus. We termed this unusual type as a "modified rapidly adapting" mechanoreceptor (MRA). 4. The response characteristics of MRAs change to those of typical RAs after a systemic injection of phentolamine, an alpha-adrenergic receptor blocker. 5. We conclude that many RAs become abnormal under the influence of sympathetic efferents in neuropathic pain, so that their response patterns change to those of MRAs. We propose that this abnormality is responsible for signaling the mechanical allodynia that can be seen in neuropathic pain states such as causalgia.

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Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8197281 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Zhiyong Wang ◽

Jianwei Wang ◽

Lihua Qin ◽

Weiguang Zhang

Keyword(s):

Neuropathic Pain ◽

Mechanical Allodynia ◽

Chronic Constriction Injury ◽

Catgut Suture ◽

Cold Allodynia ◽

Injury Model ◽

Neuropathic Pain Model ◽

Gait Function ◽

Chronic Constriction Injury Model ◽

Heat Hyperalgesia

Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

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Rufinamide alleviates mechanical allodynia in a mouse neuropathic pain model

European Journal of Anaesthesiology ◽

10.1097/00003643-201106001-00622 ◽

2011 ◽

Vol 28 ◽

pp. 193

Author(s):

M. R. Suter ◽

G. Kirschmann ◽

H. Abriel ◽

I. Decosterd

Keyword(s):

Neuropathic Pain ◽

Mechanical Allodynia ◽

Pain Model ◽

Neuropathic Pain Model

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Minocycline attenuates mechanical allodynia and expression of spinal NMDA receptor 1 subunit in rat neuropathic pain model

Journal of Physiology and Biochemistry ◽

10.1007/s13105-012-0217-4 ◽

2012 ◽

Vol 69 (3) ◽

pp. 349-357 ◽

Cited By ~ 15

Author(s):

Shaofeng Pu ◽

Yongming Xu ◽

Dongping Du ◽

Meirong Yang ◽

Xin Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Nmda Receptor ◽

Mechanical Allodynia ◽

Pain Model ◽

Neuropathic Pain Model

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A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-015-1145-y ◽

2015 ◽

Vol 388 (11) ◽

pp. 1129-1140 ◽

Cited By ~ 22

Author(s):

Gowhar Ali ◽

Fazal Subhan ◽

Muzaffar Abbas ◽

Jehan Zeb ◽

Muhammad Shahid ◽

...

Keyword(s):

Neuropathic Pain ◽

Mechanical Allodynia ◽

Diabetic Neuropathic Pain ◽

Pain Model ◽

Dynamic Mechanical ◽

Neuropathic Pain Model

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The perception threshold counterpart to dynamic and static mechanical allodynia assessed using von Frey filaments in peripheral neuropathic pain patients

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2010.08.001 ◽

2011 ◽

Vol 2 (1) ◽

pp. 9-16 ◽

Cited By ~ 4

Author(s):

Åsa H. Landerholm ◽

Per T. Hansson

Keyword(s):

Neuropathic Pain ◽

Nerve Block ◽

Mechanical Allodynia ◽

Threshold Level ◽

Mechanical Stimulus ◽

Perception Threshold ◽

Static Mechanical ◽

Continuous Nerve Block ◽

C Fibre ◽

Myelinated Fibres

AbstractBackground and aimPain due to a usually non-painful mechanical stimulus, mechanical allodynia, is an oppressive symptom in subgroups of patients with neuropathic pain. Dynamic mechanical allodynia (DMA) is evoked by a normally innocuous light moving mechanical stimulus on the skin and static mechanical allodynia (SMA) by a sustained, normally innocuous pressure against the skin. DMA is claimed to be mediated by myelinated fibres and SMA by C-fibres. Also A-delta fibres have been implicated in the static subtype. A low intensity vertically applied stimulus of 1 second (s) is expected to activate predominantly rapidly adapting A-beta mechanoreceptors thus recruiting the same peripheral substrate as a horizontally moving brush on top of the skin. In patients with SMA we assumed an activation of Cbut also A-delta fibres from a static 10 s von Frey filament stimulus. The aim was to investigate if DMA and SMA could be assessed at perception threshold level using short or longer lasting usually non-painful von Frey filament prodding of the neuropathic skin.Patients and methodsEighteen patients with painful unilateral partial peripheral traumatic nerve injury suffering from SMA (n= 9) and/or DMA (n= 18) in a limb were studied. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to pain at perception threshold level using 1 s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin.ResultsThe main outcome was the finding that elevation of vF1 and vF10 occurred simultaneously and significantly prior to an increase in the perception level to cold or warmth during the continuous nerve block. Single patients demonstrated a slight decrease in cold perception levels at the time of elevation of vF1 or vF10 and a possible contribution to mechanical allodynia from A-delta-fibres can therefore not completely be ruled out although the recorded alterations were minor. None of the patients reported an elevation of the perception level to warmth at the time of elevation of vF1 or vF10 excluding contribution from C-fibres. Further, only patients with clinically established SMA (n= 9) reported continuous pain to a sustained 10 s von Frey filament stimulation (vF10). Patients with only DMA (n= 9) reported pain merely for the initial 1–3 s of the total stimulus duration of 10 s and for a few seconds after the filament was lifted from the skin.ConclusionsThese findings support the role of A-beta fibres as peripheral mediators of both vF1 and vF10 although different receptor organs may be involved, i.e., rapidly (RA) and slowly (SA-I) adapting mechanoreceptors.ImplicationsTechniques to quantify the different allodynias at perception threshold level deserve further attention as possible adjuncts to suprathreshold stimuli in intervention studies aimed at modifying these stimulus-evoked phenomena.

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

Journal of Neurophysiology ◽

10.1152/jn.1999.81.5.2226 ◽

1999 ◽

Vol 81 (5) ◽

pp. 2226-2233 ◽

Cited By ~ 67

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.

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