Faculty Opinions recommendation of Microneurographic identification of spontaneous activity in C-nociceptors in neuropathic pain states in humans and rats.

Author(s):  
Lucy Donaldson
2013 ◽  
Vol 16 (1) ◽  
pp. 16-22 ◽  
Author(s):  
Jesse R. Moes ◽  
Janean E. Holden

The study of neuropathic pain has focused on changes within the nervous system, but little research has described systemic changes that may accompany neuropathic pain. Objective: As part of a larger project characterizing the metabolic, activity, and musculoskeletal changes associated with neuropathic pain, the objective of the current study was to characterize changes in spontaneous activity and skeletal muscle mass using an established animal model of neuropathic pain, the chronic constriction injury (CCI) model. Method: Male Sprague-Dawley rats were used in this pre- and posttest quasi-experimental study. The experimental group ( n = 13) received CCI surgery, while age- and weight-matched rats received sham surgery (SHAM; n = 5). Thermal testing verified the presence of neuropathic pain. Spontaneous cage activity was measured gravimetrically prior to and following CCI ( n = 4). Animals were euthanized and skeletal muscle was dissected and weighed to determine muscle atrophy. Results: Shorter foot withdrawal latency of the ipsilateral hind limb confirmed the presence of thermal hyperalgesia in CCI rats, a sign of neuropathic pain. Weight increased in both CCI and SHAM rats. Spontaneous activity decreased following CCI ligation. Muscles of the ipsilateral hind limb weighed significantly less than contralateral hind limb muscles in CCI rats 2 and 6 weeks after surgery. In addition, CCI rats had smaller ipsilateral hind limb muscles than SHAM rats. Conclusion: Neuropathic pain contributes to skeletal muscle atrophy and decreases in activity in rats.


Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 222-222
Author(s):  
Robert Y North ◽  
Laurence D Rhines ◽  
Claudio E Tatsui ◽  
Ganesh Rao ◽  
Patrick M Dougherty

Abstract INTRODUCTION Hyperexcitability of primary sensory neurons and its most extreme form, spontaneous activity, are key cellular-level drivers of neuropathic pain. Though extensively studied in animal models of neuropathic pain and established as a phenomenon occurring in human primary sensory neurons, this altered electrophysiology has not been rigorously studied for human primary sensory neurons nor has its relationship to clinical symptoms of neuropathic pain been established. METHODS The study was approved by the M.D. Anderson IRB. Written informed consent for participation was obtained from each tissue donor. Human dorsal root ganglia and medical histories were obtained from patients undergoing oncological spine surgery that necessitated sacrifice of spinal nerve roots as part of standard of care. Clinical data regarding presence of radicular/neuropathic pain was obtained through retrospective review of medical records or collected at time of study enrollment. Neurons were dissociated from surrounding tissue, briefly maintained in cell-culture (24-72 hours), and examined with whole-cell patch clamp techniques. RESULTS >Electrophysiological recordings were obtained from a total of 110 neurons, dissociated from 23 dorsal root ganglia, donated by 13 patients. Spontaneous activity was noted in 15% (12/79) of neurons from ganglia with pain in a corresponding dermatome vs 0% (0/31) of neurons from pain free ganglia (P < 0.05) Compared to neurons without spontaneous activity, human sensory neurons with spontaneous activity had significantly altered intrinsic membrane properties; depolarized resting membrane potential, hyperexcitability, and altered action potential kinetics (all P < 0.05). CONCLUSION Utilizing whole-cell patch clamp of dissociated human primary sensory neurons from patients both with and without neuropathic pain this study presents two important new findings: 1) first demonstration of a statistically significant association between in vitro spontaneous activity of dissociated human primary sensory neurons and neuropathic pain 2) the first characterization of the altered intrinsic membrane properties associated with spontaneous activity in human primary sensory neurons.


2021 ◽  
Author(s):  
Shaquia Idlett-Ali ◽  
Heidi Kloefkorn ◽  
William Gooslby ◽  
Shawn Hochman

Spinal cord injury (SCI) can induce dysfunction in a multitude of neural circuits including those that lead to impaired sleep, respiratory dysfunction and neuropathic pain. We used a lower thoracic rodent contusion SCI model - known to develop mechanosensory stimulus hypersensitivity, and spontaneous activity in primary afferents that associates neuropathic pain - and paired this with new approaches that enabled chronic capture of three state sleep and respiration to characterize dysfunction and assess possible interrelations. Noncontact electric field sensors were embedded into home cages for noninvasive capture in naturally behaving mice of the temporal evolution of sleep and respiration changes for 6 weeks after SCI. Hindlimb mechanosensitivity was assessed weekly, and terminal experiments measured primary afferent spontaneous activity in situ from intact lumbar dorsal root ganglia (DRG). We observed that SCI led to increased spontaneous primary afferent activity (both firing rate and the number of spontaneously active DRGs) that correlated with reduced hindpaw mechanical sensitivity, increased respiratory rate variability, and increased sleep fragmentation. This is the first study to measure and link sleep dysfunction and variability in respiratory rate in a SCI model of neuropathic pain, and thereby provide broader insight into the magnitude of overall stress burden initiated by neural circuit dysfunction after SCI.


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