title: Treatment considerations in painful HIV-related neuropathy.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP) is the most common HIV-associated sensory neuropathy. The envelope glycoprotein of HIV-1, gp 120, appears to contribute to this painful neuropathy. Two standard treatments for HIV infection/HIV-related painful DSP (e.g., antiviral therapy [e.g., nucleoside reverse transcriptase inhibitors (NRTI)] opioids) should each be carefully evaluated prior to being utilized to ameliorate the pain of DSP, since they may actually promote nociception. Nucleoside reverse transcriptase inhibitors require activation in the cell via the addition of 3 phosphate groups (by cellular kinases) to their deoxyribose moiety, to form NRTI triphosphates. Subsequently, these deoxynucleotide analogs compete with natural deoxynucleotides for incorporation into the growing viral DNA chain. The incorporation of NRTIs into the viral DNA chain leads to chain termination; since the nucleoside reverse transcriptase inhibitors lack a 3'-hydroxyl group on the deoxyribose moiety (unlike natural deoxynucleotides), so that the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy. Although there is no robust data, there does seem to be information which would support the notion of opioids having increased risk of being particularly pronociceptive when being used to treat painful HIV-related neuropathy. It thus appears conceivable that the use of at least certain opioids in efforts to achieve analgesia in patients with painful HIV-related neuropathy may be less than ideal since at least certain opioid analgesics themselves may potentially contribute to "fueling the fire" of HIV enhanced pain hypersensitivity; at least in part via upregulation of specific chemokine receptors (e.g., CXCR4) which seem to be vitally important in promoting HIV-related pain facilitation. The risk benefit ratio of treatment with agents such as NRTIs as well as opioids should be reviewed for specific individual patients, prior to clinicians initiating these agents.
  
  
  OBJECTIVE
  To raise awareness of the theoretical potential downside that opioids may possess if they are used for the treatment of painful HIV-related neuropathy.
  
  
  METHODS
  A narrative review of selected literature.
  
  
  CONCLUSIONS
  Hypothetical in nature.
  
  
  CONCLUSIONS
  Clinicians should consider all aspects of various therapeutic options, carefully weighing the risk/benefit ratios of each potential treatment before initiating opioids for painful HIV-related neuropathy.
authors.affiliation: Albany Medical College, Department of Anesthesiology, Albany, NY, USA. smithh@mail.amc.edu
authors.forename: Howard S
authors.initials: HS
authors.lastname: Smith
mesh_terms: D000075202:Contraindications; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D007049:Iatrogenic Disease / Q000517:prevention & control*; D009437:Neuralgia / Q000139:chemically induced* / Q000503:physiopathology / Q000821:virology*; D009619:Nociceptors / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
chemical_list: D018894:Reverse Transcriptase Inhibitors