Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors

Abstract

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey’s test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4–L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

<p>Long Noncoding RNA H19 Induces Neuropathic Pain by Upregulating Cyclin-Dependent Kinase 5-Mediated Phosphorylation of cAMP Response Element Binding Protein</p>

“…33 In NC model rats where substance P was injected, GFAP decreased as mechanical allodynia was mitigated; on the other hand, anti-inflammatory factors were actively expressed. 34 Moreover, 5-HT 2A has the ability to increase potassium chloride cotransporter type 2, thereby mediating motoneuronal inhibition and alleviating NP induced by spinal cord injury. 35 GABA B2, which plays a role in maintaining the analgesic function of opioid oxycodone, was reduced with nerve injury.…”

Ion Channels Involved in Substance P-Mediated Nociception and Antinociception

“…In 1980, Oehme et al suggested that SP produced naloxone-reversed analgesia in mice with high sensitivity to thermal stimulation but induced hyperalgesia in mice with low sensitivity to thermal stimulation [41]. In addition, SP has been found to effectively reduce neuropathic pain [42] and inflammatory pain [43]. To sum up, these studies demonstrated that SP can regulates opioid-dependent analgesic effects in distinct cell types, probably via different receptors.…”

The neuropathic pain: An overview of the current treatment and future therapeutic approaches

“…SP might represent a good drug candidate for neuropathic pain management; however, further investigations should be performed to determine its exact mechanism of action. 23 Natural compounds have been investigated for the management of many diseases, and some of them may present therapeutic candidates for the development of new drugs to alleviate neuropathic pain.…”

“…SP might represent a good drug candidate for neuropathic pain management; however, further investigations should be performed to determine its exact mechanism of action. 23 …”