Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks - PubMed (original) (raw)

Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks

Chelsea C Hays Weeks et al. Front Pain Res (Lausanne). 2022.

Abstract

HIV-associated distal neuropathic pain (DNP) is one of the most prevalent, disabling, and treatment-resistant complications of HIV, but its biological underpinnings are incompletely understood. While data specific to mechanisms underlying HIV DNP are scarce, functional neuroimaging of chronic pain more broadly implicates the role of altered resting-state functional connectivity within and between salience network (SN) and default mode network (DMN) regions. However, it remains unclear the extent to which HIV DNP is associated with similar alterations in connectivity. The current study aimed to bridge this gap in the literature through examination of resting-state functional connectivity patterns within SN and DMN regions among people with HIV (PWH) with and without DNP. Resting state functional magnetic resonance imaging (rs-fMRI) scans were completed among 62 PWH with HIV-associated peripheral neuropathy, of whom 27 reported current DNP and 35 did not. Using subgrouping group iterative multiple estimation, we compared connectivity patterns in those with current DNP to those without. We observed weaker connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) and stronger connectivity between the anterior cingulate cortex (ACC) and thalamus among those reporting DNP. Overall, these findings implicate altered within DMN (i.e., MPFC-PCC) and within SN (i.e., ACC-thalamus) connectivity as potential manifestations of adaptation to pain from neuropathy and/or mechanisms underlying the development/maintenance of DNP. Findings are discussed in the context of differential brain response to pain (i.e., mind wandering, pain aversion, pain facilitation/inhibition) and therapeutic implications.

Keywords: HIV; default mode network; fMRI; functional connectivity; neuropathic pain.

© 2022 Hays Weeks, Simmons, Strigo, Timtim, Ellis and Keltner.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1

Figure 1

GIMME results. The DNP+group was characterized by functional connectivity between the thalamus and ACC, whereas the DNP− group was characterized by connectivity between the MPFC and PCC. Both groups demonstrated connectivity between the MPFC and ACC, ACC and PCC, ACC and insula, and PCC and thalamus. Note: MPFC, medial prefrontal cortex; ACC, anterior cingulate cortex; PCC, posterior cingulate cortex.

Figure 2

Figure 2

Connectivity subgroup differences in group-level paths. DNP+ had a greater MPFC to ACC path and a lower thalamus to PCC path, compared to subgroup DNP−. *p <0.05 (uncorrected). Note: MPFC, medial prefrontal cortex; ACC, anterior cingulate cortex; LINS, left insula; PCC, posterior cingulate cortex; Thal, thalamus.

References

    1. Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, et al. CHARTER Study group. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER study. Arch Neurol. (2010) 67:552–8. 10.1001/archneurol.2010.76 -DOI -PMC -PubMed
    1. Verma S, Estanislao L, Mintz L, Simpson D. Controlling neuropathic pain in HIV. Curr Infect Dis Rep. (2004) 6:237–42. 10.1007/s11908-004-0014-5 -DOI -PubMed
    1. Robinson-Papp J, Morgello S, Vaida F, Fitzsimons C, Simpson DM, Elliott KJ, et al. Association of self-reported painful symptoms with clinical and neurophysiologic signs in HIV-associated sensory neuropathy. Pain. (2010) 151:732–6. 10.1016/j.pain.2010.08.045 -DOI -PMC -PubMed
    1. Castillo D, Ernst T, Cunningham E, Chang L. Altered associations between pain symptoms and brain morphometry in the pain matrix of HIV-seropositive individuals. J Neuroimmune Pharmacol. (2018) 13:77–89. 10.1007/s11481-017-9762-5 -DOI -PMC -PubMed
    1. Keltner JR, Fennema-Notestine C, Vaida F, Wang D, Franklin DR, Dworkin RH, et al. HIV-Associated Distal neuropathic pain is associated with smaller total cerebral cortical gray matter. J Neurovirol. (2014) 20:209–18. 10.1007/s13365-014-0236-8 -DOI -PMC -PubMed

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