Abstract
An injury to peripheral nerves leads to skin denervation, which often is followed by increased pain sensitivity of the denervated areas and the development of neuropathic pain. Changes in innervation patterns during the reinnervation process of the denervated skin could contribute to the development of neuropathic pain. Here, we examined the changes in the innervation pattern during reinnervation and correlated them with the symptoms of neuropathic pain. Using a multispectral labeling technique—PainBow, which we developed, we characterized dorsal root ganglion (DRG) neurons innervating distinct areas of the rats’ paw. We then used spared nerve injury, causing partial denervation of the paw, and examined the changes in innervation patterns of the denervated areas during the development of allodynia and hyperalgesia. We found that, differently from normal conditions, during the development of neuropathic pain, these areas were mainly innervated by large, non-nociceptive neurons. Moreover, we found that the development of neuropathic pain is correlated with an overall decrease in the number of DRG neurons innervating these areas. Importantly, treatment with ouabain facilitated reinnervation and alleviated neuropathic pain. Our results suggest that local changes in peripheral innervation following denervation contribute to neuropathic pain development. The reversal of these changes decreases neuropathic pain.
Highlights
Chronic neuropathic pain is characterized by hyperalgesia, allodynia, and prolonged episodes of spontaneous pain [1,2]
The number of cells that innervate innervating specific tissue areas. This approach is based on the injection to a target organ of multiple spectrally separated fluorescent dyes that were conjugated to Wheat Germ Agglutinin (WGA), which were retrogradely transported to cell somata by the axons innervating the target organs
We aimed to identify the dorsal root ganglion (DRG) neurons whose axons sprout to the denervated areas of the paw in the model of spared nerve injury (SNI)
Summary
Chronic neuropathic pain is characterized by hyperalgesia (hypersensitivity to noxious stimuli), allodynia (the sensation of pain to innocuous stimuli), and prolonged episodes of spontaneous pain [1,2]. The abnormal activity of injured peripheral nerves triggers hyperexcitable changes in the central nervous system, known as central sensitization, which is the key factor in the development of neuropathic pain [4,5]. The injury of peripheral nerves causes the denervation of body areas innervated by these nerves. A behavioral study that examined changes in the mechanical threshold in denervated paw following a complete section of the sciatic nerve showed that reinnervation begins within a week after injury [12]. This study suggests that reinnervation originated from a collateral sprouting of high-threshold mechanoreceptors from the intact saphenous nerve, which invaded the denervating skin, leading to the development of mechanical allodynia [12]. Histological and immunohistochemical studies on excised paw skins of rats following a loose ligation of the common sciatic nerve or spared nerve injury (SNI) demonstrate
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
