Marzia Malcangio, King's College London
This comment was coauthored by Andrew Rice, Imperial College London.
This timely study provides evidence for astrogliosis in post mortem spinal cord of a small number HIV-positive patients with a history of chronic pain and post mortem histologically proven peripheral neuropathy, but not in tissues obtained from HIV patients with no chronic pain or healthy controls . It is important to note that most of the HIV-positive patients from whom tissue was taken died of AIDS related illnesses and therefore had advanced disease; a rather different clinical picture to today’s HIV-positive patients who usually have their HIV infection adequately supressed by modern antiretroviral drugs. These patients by comparison are relatively healthy, although around 40% have painful polyneuropathy. Furthermore, most of the patients from whom tissue was obtained had been exposed to the neurotoxic nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral drugs which known to be associated with painful peripheral neuropathy, but which are now rarely employed in well-resourced settings.
The increase in astroglial markers is associated with increased levels of pro-inflammatory cytokines as well as intracellular MAP kinases which are considered as markers for pain facilitation in the spinal cord. This is compatible with preclinical evidence which suggests that astrocytosis is associated with the maintenance of neuropathic pain, whereas in non traumatic neuropathy microglia have a negligible role in the generation of neuropathic pain, especially past the initial injury phase.
These initial pilot findings are interesting and provide several pieces of evidence suggesting that aspects of pre-clinical models are approaching a state of refinement that begins to approximate to the human conditions. However, these findings need to be replicated in tissues from a larger cohort of well phenotyped patients who reflect the modern day clinical presentation of HIV-associated painful sensory distal symmetrical polyneuropathy.
Ru-Rong Ji, Duke University Medical Center
This is an important paper showing glial activation in human spinal cord in a chronic pain condition. It is also very interesting to demonstrate that HIV-induced neuropathic pain, in the late-phase, is associated with astroglial reaction but not microglial reaction. Furthermore, this paper demonstrated that chronic pain is associated with MAPK activation, which is known to regulate glial signaling and production of proinflammatory cytokines.
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