Perineural application of resiniferatoxin on uninjured L3 and L4 nerves completely alleviates thermal and mechanical hypersensitivity following L5 nerve injury in rats

Javed, Hayate; Rehmathulla, Sumisha; Tariq, Saeed; Emerald, Bright Starling; Ljubisavljević, Miloš; Shehab, Safa

doi:10.1002/cne.24884

Cited by 8 publications

(52 citation statements)

References 66 publications

(97 reference statements)

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“…Further evidence was supported by the distributions of these populations in distinct but overlapping regions, demonstrating that CGRP is mainly terminating in the laminae I and IIo, whereas IB4 binding is mainly localized in lamina II (Javed et al, 2020;Kitchener et al, 1994;Wang et al, 1994). When IB4 was used as a neuroanatomical tracer, injection into the sciatic nerve or lumbar spinal nerves resulted in IB4 labeling mainly located in the center of lamina II leaving a small ventral area of IIi unlabeled (Shehab, 2009;Shehab & Hughes, 2011;Shehab et al, 2008).…”

Section: Nociceptive Markers In the Drg Of Mouse Rat Human And Camelmentioning

confidence: 89%

“…Camel (current study) Nonpeptidergic (IB4/P2X3R) 29.6% (Price & Flores, 2007); 38.5% (Javed et al, 2020).…”

Section: Rat Mice Humanmentioning

confidence: 90%

“…In a preliminary experiment, we have attempted to reveal the expression of TRPV1 in the DRG and spinal cord of camel with immunohistochemistry and western blotting techniques by using rabbit polyclonal TRPV1 (ENZO Life Sciences, Lausen, Switzerland) and guinea pig polyclonal TRPV1 (Neuromics, Edina, MN, USA) antibodies. Although these antibodies recognize TRPV1 expression in DRG or spinal cord in rats (Javed et al, 2020) and mice (Javed and Shehab, unpublished data), both failed to recognize the expression of TRPV1 in the camel spinal cord and DRG.…”

mentioning

confidence: 99%

“…Although the neurochemical anatomy of the DRG and spinal cord has been widely investigated in rodents (Averill et al, 1995;Gerke & Plenderleith, 2002;Guo et al, 1999;Javed et al, 2020;Nagy & Hunt, 1982;Price & Flores, 2007;Shiers et al, 2020, Todd, 2010, 2016Zwick et al, 2002), and to a certain extent in different mammalian species such as monkeys (Torres-da-Silva et al, 2016;Zhang et al, 1993), cats (Traub et al, 1990), horses (Russo et al, 2011), and guinea pigs (Lawson et al, 1997), and recently in humans (Shiers et al, 2021), no similar work has been performed in camels.…”

mentioning

confidence: 99%

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Co‐localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel

Javed

Rehmathulla

Tariq

et al. 2021

J of Comparative Neurology

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Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP-and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1-and NOS-immunoreactive neurons, respectively, were also colocalized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were colocalized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

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Section: Nociceptive Markers In the Drg Of Mouse Rat Human And Camelmentioning

confidence: 89%

“…Camel (current study) Nonpeptidergic (IB4/P2X3R) 29.6% (Price & Flores, 2007); 38.5% (Javed et al, 2020).…”

Section: Rat Mice Humanmentioning

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Co‐localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel

Javed

Rehmathulla

Tariq

et al. 2021

J of Comparative Neurology

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“…However increased TrpV1 expression was seen in uninjured neurons, including small diameter C fibers, along with ectopic expression in large diameter-A fibers (Hudson et al, 2001). The contribution of uninjured DRG to stimulusevoked pain is underscored by the fact that chemical ablation of TrpV1-expressing neurons of uninjured L3 and L4 nerves could completely alleviate thermal hyperalgesia and mechanical allodynia after L5 SNL (Javed et al, 2020).…”

Section: Transient Receptor Potential Cation Channel Vanilloid Type 1mentioning

confidence: 99%

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

Tran

Crawford

2020

Front. Cell. Neurosci.

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Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.

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Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury

et al. 2020

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Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

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Perineural application of resiniferatoxin on uninjured L3 and L4 nerves completely alleviates thermal and mechanical hypersensitivity following L5 nerve injury in rats

Cited by 8 publications

References 66 publications

Co‐localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel

Co‐localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury

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