Learned Avoidance From Noxious Mechanical Simulation But Not Threshold Semmes Weinstein Filament Stimulation After Nerve Injury in Rats

Wu, Hsiang‐En; Gemes, Geza; Zoga, Vasiliki; Kawano, Takashi; Hogan, Quinn H.

doi:10.1016/j.jpain.2009.07.011

Cited by 63 publications

(55 citation statements)

References 32 publications

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“…Finally, a subpopulation of A␤ neurons naturally convey a nociceptive modality (Djouhri and Lawson, 2004). These units have central processes that project to the superficial dorsal horn (Light and Perl, 1979;Woodbury et al, 2008), express TrkA (Fang et al, 2005), and lack complex tactile organs at their peripheral terminals (Kruger et al, 1981), unlike our transduced A␤-LTMR population. However, we cannot exclude a contribution from A␤ nociceptors.…”

Section: Discussionmentioning

confidence: 96%

CaMKII Controls Whether Touch Is Painful

Yu¹,

Pan²,

Weyer

et al. 2015

J. Neurosci.

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The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (A␤-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of A␤-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in A␤-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic A␤-LTMRs removes dorsal horn inhibition that otherwise prevents A␤-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in A␤-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. We conclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions.

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Section: Discussionmentioning

confidence: 96%

CaMKII Controls Whether Touch Is Painful

Yu¹,

Pan²,

Weyer

et al. 2015

J. Neurosci.

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“…Reflex withdrawal from tactile or thermal stimuli is a spinal reflex. However, animal experiences cannot be relied on and painful tests are therefore used for confirmation (40). Validation of pain in animals is controversial.…”

Section: Discussionmentioning

confidence: 99%

Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

et al. 2017

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Background/aim: Chronic migraine is a common debilitating disease with limited treatment options. We aimed to develop a novel model for chronic migraine by ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to exacerbate acute headache attacks. Materials and methods: Exacerbation of the headache was induced by NTG (10 mg/kg, subcutaneously) administered to male Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold allodynia was tested using Von Frey (VF) filaments and acetone, respectively. Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were investigated. Results: NTG administration significantly decreased VF threshold values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw (P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P = 0.013). The number/rate of entrance to open arms in the EPM was significantly decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 ± 4.7, contralateral 11.8 ± 1.9, P < 0.05) in chronic NCN-ligated rats exposed to acute NTG. Conclusion:The presented model provides a valid chronic migraine model relevant to humans, as NTG challenge in chronic NCL rats generated lateralized headache with cephalic and extracephalic allodynia, altered cold sensitivity, anxiety, and neuronal activation in the nociceptive laminae of brainstem trigeminal pain nuclei.

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“…We measured the incidence of a pattern of noxious stimulus-induced hyperalgesic behavior, which is a specific neuropathic-related pain behavior that we have previously documented to be associated with conditioned place avoidance (Hogan et al, 2004;Wu et al, 2010). Thus, noxious stimulation (22G spinal needle) was used as only inclusion criterion after peripheral nerve injury.…”

Section: Methodsmentioning

confidence: 99%

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca2+ Current in Sensory Neurons

Pan

Guo

Kwok

et al. 2014

The Journal of Pharmacology and Experimental Therapeutics

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Sigma-1 receptor (s1R), an endoplasmic reticulum-chaperone protein, can modulate painful response after peripheral nerve injury. We have demonstrated that voltage-gated calcium current is inhibited in axotomized sensory neurons. We examined whether s1R contributes to the sensory dysfunction of voltagegated calcium channel (VGCC) after peripheral nerve injury through electrophysiological approach in dissociated rat dorsal root ganglion (DRG) neurons. Animals received either skin incision (Control) or spinal nerve ligation (SNL). Both s1R agonists, (1)pentazocine (PTZ) and DTG [1,3-di-(2-tolyl)guanidine], dose dependently inhibited calcium current (I Ca ) with Ba 21 as charge carrier in control sensory neurons. The inhibitory effect of s1R agonists on I Ca was blocked by s1R antagonist, BD1063(1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar effect on I Ca in axotomized fifth DRG neurons (SNL L5). Both PTZ and DTG shifted the voltage-dependent activation and steady-state inactivation of VGCC to the left and accelerated VGCC inactivation rate in both Control and axotomized L5 SNL DRG neurons. The s1R antagonist, BD1063 (10 mM), increases I Ca in SNL L5 neurons but had no effect on Control and noninjured fourth lumbar neurons in SNL rats. Together, the findings suggest that activation of sR1 decreases I Ca in sensory neurons and may play a pivotal role in pain generation.

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Learned Avoidance From Noxious Mechanical Simulation But Not Threshold Semmes Weinstein Filament Stimulation After Nerve Injury in Rats

Cited by 63 publications

References 32 publications

CaMKII Controls Whether Touch Is Painful

CaMKII Controls Whether Touch Is Painful

Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated rats: implications for chronic migraine

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca2+ Current in Sensory Neurons

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