scholarly journals The Role of the Periaqueductal Gray in the Modulation of Pain in Males and Females: Are the Anatomy and Physiology Really that Different?

2009 ◽  
Vol 2009 ◽  
pp. 1-12 ◽  
Author(s):  
Dayna R. Loyd ◽  
Anne Z. Murphy

Anatomical and physiological studies conducted in the 1960s identified the periaqueductal gray (PAG) and its descending projections to the rostral ventromedial medulla (RVM) and spinal cord dorsal horn, as a primary anatomical pathway mediating opioid-based analgesia. Since these initial studies, the PAG-RVM-spinal cord pathway has been characterized anatomically and physiologically in a wide range of vertebrate species. Remarkably, the majority of these studies were conducted exclusively in males with the implicit assumption that the anatomy and physiology of this circuit were the same in females; however, this is not the case. It is well established that morphine administration produces greater antinociception in males compared to females. Recent studies indicate that the PAG-RVM pathway contributes to the sexually dimorphic actions of morphine. This manuscript will review our anatomical, physiological, and behavioral data identifying sex differences in the PAG-RVM pathway, focusing on its role in pain modulation and morphine analgesia.

2019 ◽  
Vol 17 (12) ◽  
pp. 1133-1145 ◽  
Author(s):  
Rita Bardoni

Background: Despite the extensive number of studies performed in the last 50 years, aimed at describing the role of serotonin and its receptors in pain modulation at the spinal cord level, several aspects are still not entirely understood. The interpretation of these results is often complicated by the use of different pain models and animal species, together with the lack of highly selective agonists and antagonists binding to serotonin receptors. Method: In this review, a search has been conducted on studies investigating the modulatory action exerted by serotonin on specific neurons and circuits in the spinal cord dorsal horn. Particular attention has been paid to studies employing electrophysiological techniques, both in vivo and in vitro. Conclusion: The effects of serotonin on pain transmission in dorsal horn depend on several factors, including the type of receptors activated and the populations of neurons involved. Recently, studies performed by activating and/or recording from identified neurons have importantly contributed to the understanding of serotonergic modulation on dorsal horn circuits.


Neuron ◽  
2014 ◽  
Vol 81 (6) ◽  
pp. 1443 ◽  
Author(s):  
Rita Bardoni ◽  
Vivianne L. Tawfik ◽  
Dong Wang ◽  
Amaury François ◽  
Carlos Solorzano ◽  
...  

2008 ◽  
Vol 109 (5) ◽  
pp. 879-889 ◽  
Author(s):  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Seo-Yeon Yoon ◽  
Hyoung-Sig Seo ◽  
Young-Bae Kwon ◽  
...  

Background Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Methods Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. Results BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. Conclusions These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.


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