Evidence for lack of direct causality between pain and affective disturbances in a rat peripheral neuropathy model |
| |
Authors: | Marco R Guimares Ana R Soares Ana M Cunha Madalena Esteves Snia Borges Ricardo Magalhes Pedro S Moreira Ana J Rodrigues Nuno Sousa Armando Almeida Hugo Leite‐Almeida |
| |
Institution: | Marco R. Guimarães,Ana R. Soares,Ana M. Cunha,Madalena Esteves,Sónia Borges,Ricardo Magalhães,Pedro S. Moreira,Ana J. Rodrigues,Nuno Sousa,Armando Almeida,Hugo Leite‐Almeida |
| |
Abstract: | Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague‐Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury SNI]) and compared their performance in a battery of behavioral paradigms—anxiety, depression and fear memory—with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold LT]), but 13% were similar to Sham controls (high threshold HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI‐L) and right (SNI‐R) lesions and the lack of association between pain and behavior still remains. Left‐lesioned animals, independent of the LT or HT phenotype, presented increased anxiety‐like behaviors and decreased well‐being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes. |
| |
Keywords: | allodynia anxiety impulsivity laterality neuropathic pain peripheral neuropathy |
|
|