Publicação
The prefrontal cortex and chronic pain : the role of metabotropic glutamatergic receptors in the descending modulation of pain
| Resumo: | In osteoarthritis (OA) the progressive degeneration of articular structures persistently activates nociceptors leading to chonic pain and subsequent cognitive and emotional impairments. Amongst the several supraspinal nuclei involved in the modulation of nociception, the medial prefrontal cortex (mPFC), a brain area part of the limbic system, is known to mediate nociception as well as emotional and cognitive functions. In addition, metabotropic glutamate receptors (mGLUR), greatly expressed in the PFC, play an important role in the neuroplasticity of brain circuits in persistent pain disorders. Amongst the three groups of mGLURs, group I (mGLUR1 and mGLUR5) increase neuronal excitability in chronic pain. In order to evaluate the role of infralimbic cortex (IL) mGLUR5 in the facilitation of nociception, we activated and inhibited the IL with specific and unspecific agonists and antagonists of mGLUR5 while (i) behaviourally assessing nociception, (ii) analysing c-Fos expression in brainstem areas involved in the modulation of nociception with and without noxious peripheral stimulation and (iii) recording neuronal activity in the rostral ventromedial medulla (RVM) of control (SHAM) and osteoarthritic (ARTH) animals. Our data showed the activation of IL mGluR5 receptors induced behavioural hyperalgesia in both experimental groups while its inhibition an antinociceptive effect in ARTH animals. Regarding c-Fos expression, the ipsilateral ventrolateral periaqueductal gray matter (VLPAG) and the dorsal part of the dorsal raphe nucleus (DRD) displayed a greater number of c-Fos expressing cells in ARTH animals when compared to SHAM animals with noxious stimulation enhancing c-Fos expression in the RVM of SHAM animals. Activating IL mGLUR5 increased c-Fos expression in the DRD, RVM and dorsal reticular nucleus (DRt) of SHAM animals and in the VLPAG of ARTH animals. The combination of pharmacological and mechanical stimuli increased c-Fos expression in the ipsilateral LC and RVM of SHAM animals and the contralateral DRt of ARTH animals. Data from the electrophysiological recordings showed antinociceptive ON- and pronociceptive OFF-like cells of the RVM are not involved in descending facilitation after the activation of IL mGLUR5. In the present work a facilitatory role of mGLUR5 upon behavioural nociception has been clearly demonstrated, further studies are however needed to understand the potential role of the RVM and DRt in mediating its effect. |
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| Autores principais: | Teixeira, Cristiana Ribeiro Silva |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | In osteoarthritis (OA) the progressive degeneration of articular structures persistently activates nociceptors leading to chonic pain and subsequent cognitive and emotional impairments. Amongst the several supraspinal nuclei involved in the modulation of nociception, the medial prefrontal cortex (mPFC), a brain area part of the limbic system, is known to mediate nociception as well as emotional and cognitive functions. In addition, metabotropic glutamate receptors (mGLUR), greatly expressed in the PFC, play an important role in the neuroplasticity of brain circuits in persistent pain disorders. Amongst the three groups of mGLURs, group I (mGLUR1 and mGLUR5) increase neuronal excitability in chronic pain. In order to evaluate the role of infralimbic cortex (IL) mGLUR5 in the facilitation of nociception, we activated and inhibited the IL with specific and unspecific agonists and antagonists of mGLUR5 while (i) behaviourally assessing nociception, (ii) analysing c-Fos expression in brainstem areas involved in the modulation of nociception with and without noxious peripheral stimulation and (iii) recording neuronal activity in the rostral ventromedial medulla (RVM) of control (SHAM) and osteoarthritic (ARTH) animals. Our data showed the activation of IL mGluR5 receptors induced behavioural hyperalgesia in both experimental groups while its inhibition an antinociceptive effect in ARTH animals. Regarding c-Fos expression, the ipsilateral ventrolateral periaqueductal gray matter (VLPAG) and the dorsal part of the dorsal raphe nucleus (DRD) displayed a greater number of c-Fos expressing cells in ARTH animals when compared to SHAM animals with noxious stimulation enhancing c-Fos expression in the RVM of SHAM animals. Activating IL mGLUR5 increased c-Fos expression in the DRD, RVM and dorsal reticular nucleus (DRt) of SHAM animals and in the VLPAG of ARTH animals. The combination of pharmacological and mechanical stimuli increased c-Fos expression in the ipsilateral LC and RVM of SHAM animals and the contralateral DRt of ARTH animals. Data from the electrophysiological recordings showed antinociceptive ON- and pronociceptive OFF-like cells of the RVM are not involved in descending facilitation after the activation of IL mGLUR5. In the present work a facilitatory role of mGLUR5 upon behavioural nociception has been clearly demonstrated, further studies are however needed to understand the potential role of the RVM and DRt in mediating its effect. |
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