scholarly journals Aromatase Inhibition Exacerbates Pain and Reactive Gliosis in the Dorsal Horn of the Spinal Cord of Female Rats Caused by Spinothalamic Tract Injury

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4341-4355 ◽  
Author(s):  
Samar Ghorbanpoor ◽  
Luis Miguel Garcia-Segura ◽  
Ali Haeri-Rohani ◽  
Fariba Khodagholi ◽  
Masoumeh Jorjani

Abstract Central pain syndrome is characterized by severe and excruciating pain resulting from a lesion in the central nervous system. Previous studies have shown that estradiol decreases pain and that inhibitors of the enzyme aromatase, which synthesizes estradiol from aromatizable androgens, increases pain sensitivity. In this study we have assessed whether aromatase expression in the dorsal horns of the spinal cord is altered in a rat model of central pain syndrome, induced by the unilateral electrolytic lesion of the spinothalamic tract. Protein and mRNA levels of aromatase, as well as the protein and mRNA levels of estrogen receptors α and β, were increased in the dorsal horn of female rats after spinothalamic tract injury, suggesting that the injury increased estradiol synthesis and signaling in the dorsal horn. To determine whether the increased aromatase expression in this pain model may participate in the control of pain, mechanical allodynia thresholds were determined in both hind paws after the intrathecal administration of letrozole, an aromatase inhibitor. Aromatase inhibition enhanced mechanical allodynia in both hind paws. Because estradiol is known to regulate gliosis we assessed whether the spinothalamic tract injury and aromatase inhibition regulated gliosis in the dorsal horn. The proportion of microglia with a reactive phenotype and the number of glial fibrillary acidic protein–immunoreactive astrocytes were increased by the injury in the dorsal horn. Aromatase inhibition enhanced the effect of the injury on gliosis. Furthermore, a significant a positive correlation of mechanical allodynia and gliosis in the dorsal horn was detected. These findings suggest that aromatase is up-regulated in the dorsal horn in a model of central pain syndrome and that aromatase activity in the spinal cord reduces mechanical allodynia by controlling reactive gliosis in the dorsal horn.

2010 ◽  
Vol 103 (6) ◽  
pp. 3044-3053 ◽  
Author(s):  
Peter D. Murray ◽  
Radi Masri ◽  
Asaf Keller

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.


2018 ◽  
Vol 25 (3-4) ◽  
pp. 99-103
Author(s):  
A. E Yakovlev

Central pain syndrome (CPS) is a neurological disorder caused by damage or dysfunction of the central nervous system. Both conservative and operative methods of treatment are used in its treatment, but in most cases their effectiveness is rather low. We are presenting the clinical observation of a 60-year-old patient with spinal cord injury at the level of Th10 due to a car accident that occurred 44 years before the treatment in our clinic, who suffered from phantom pain that occurred after bilateral above the knee amputation because of advanced peripheral vascular disease. Due to the ineffectiveness of the conservative treatment, it was decided to proceed with spinal cord stimulation. The presence of pronounced postoperative changes in the area of spinal cord injury has complicated the transcutaneous placement of trial leads at the L1-L2 and Th12-L1 level. We managed to introduce leads at the level of Th7-Th8 and position them at the level of Th5-Th7. During continuous neurostimulation the pain in the sacrum, in the area of the hip joints, the phantom pain was relieved. The patient stopped using all pain medications. Spinal cord stimulation can be utilized as an alternative treatment for patients with intractable CPS.


2012 ◽  
Vol 49 (3) ◽  
pp. 470-479 ◽  
Author(s):  
Kobra Naseri ◽  
Elham Saghaei ◽  
Fatemeh Abbaszadeh ◽  
Mina Afhami ◽  
Ali Haeri ◽  
...  

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.


Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 145 ◽  
Author(s):  
Jang ◽  
Kwon ◽  
Lee

Objectives: We report on a patient with whiplash injury who had central pain, due to injury of the spinothalamic tract (STT), but who was misdiagnosed as complex regional pain syndrome (CRPS). Case description: While a minivan in which a 43-year-old female was seated in the passenger seat was stopped for a signal, a truck collided with the minivan from behind, and the minivan then repeatedly collided with trucks in front and behind the minivan. Her head repeatedly struck the minivan seat resulting in whiplash injuries. After onset, she felt pain in both legs with mild motor weakness in all four extremities and memory impairment. Eight years after onset, she was diagnosed at a university hospital as CRPS type 1 with the clinical features of hyperalgesia and mild edema and motor weakness of both legs. She visited another university hospital nine years after onset and complained of pain in the right arm and both legs, constant tingling and burning pain along with allodynia and hyperalgesia. She also showed mild weakness in the four extremities, mild edema of both legs, and memory impairment. On diffusion tensor tractography (DTT), the left spinothalamic tract (STT) showed marked narrowing, and the right STT revealed mild narrowing and partial tearing. In addition, partial tears were observed in both corticospinal tracts and the right corticoreticulospinal tract. Discontinuations were observed in the left corticoreticulospinal tract and the left fornical crus. Conclusion: Injury of the STT was demonstrated on DTT in a patient with central pain following whiplash injury. Previously, the patient was misdiagnosed as CRPS.


2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 127-127
Author(s):  
Thomas J. Smith ◽  
David Kamson ◽  
Maureen A Mealy ◽  
Steve D'Amato

127 Background: Central pain caused by spinal cord or brain injury tends to be severe and refractory despite aggressive treatment, such as in thalamic pain syndrome, neuromyelitis optica spectrum disorder (NMOSD) and other forms of transverse myelitis, and spinal cord gliomas. Methods: We reviewed our experience with treatment of these relatively rare maladies with Scrambler Therapy, a noninvasive form of neuromodulation. Results: One transverse myelitis patient got substantial relief lasting months (Mealy M, Int J MS Care. 201), leading to the NMOSD trial. In a small, sham-controlled randomized trial, NMOSD patient pain scores were reduced in the ST arm from 5 to 1.5 at 30 days, P< 0.01, while the sham treatment gave no relief. (Neurology, resubmitted) Of three patients with pain due to thalamic strokes, surgery and/or radiation, treatment gave over 50% relief long-term in 2 of 3 (D’Amato S, A A Pract. 2018). In the one spinal cord glioma patient, pain in her index finger was reduced from 8-10/10 to 1-2/10 and treatment is ongoing. All successfully treated patients reported marked relief of allodynia and hyperalgesia, in addition to pain relief as reported previously (Marineo G, JPSM 2012). Conclusions: Scrambler therapy is a promising treatment modality for patients with these individually rare but collectively common forms of central pain. It has allowed return to more normal function in most patients, with reductions in pain medication use. Pictures of electrode placement and treatment plans will be shown, allowing others to do this safe and often effective treatment. Clinical trial information: NCT03452176.


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