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HIV-associated painful polyneuropathy

  • Andrew S.C. Rice
Published/Copyright: July 1, 2012
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Scandinavian Journal of Pain
From the journal Scandinavian Journal of Pain Volume 3 Issue 3

According to WHO/UNAIDS data, there are approximately 33 million people in the world who are currently living with HIV, with the major burden of disease affecting low/middle resource communities in sub-Saharan Africa, Asia and South America. In the Scandinavian/Nordic countries, where there are effective infection prevention programmes and essentially full antiretroviral (ARV) drug access, there are ~24,000 people living with HIV (prevalence ~0.1-0.4%). A success story has been the advent of combined ARV therapy, which is now available to essentially all patients in wealthy countries and an increasing number of people in low and middle resource regions. This advance is converting HIV infection from a largely fatal disease (via the manifestations of AIDS), into a controlled chronic illness where people live relatively normal lives, and perhaps even normal life expectancies (although it is too early to tell), as a result of undetectable viral loads and lack of suppression of CD4 cell function. Therefore, a major issue in the management of people living with HIV is now the control of quality of life-limiting symptoms resulting from the manifestations of HIV infection which are either not suppressed by ARV therapy or occur as a result of the adverse effects of ARV drugs. Thus, although new infection rates may be decreasing, the increasing number of HIV positive people surviving by accessing effective ARV therapy implies an increasing healthcare burden.

Data from both high and poor resource settings indicates that HIV-associated peripheral sensory polyneuropathy (HIV-SN), usually accompanied by neuropathic pain, afflicts ~40% HIV positive people whose infection is otherwise well suppressed by ARV drugs. This makes HIV-SN one of the most prevalent manifestations of HIV infection in the ARV era and thus it will assume increasing healthcare importance as global access to ARVs continues to improve. Although, particularly in the context of AIDS, many, often exotic, mono- and poly-peripheral neuropathies have been described as being associated with HIV infection, HIV-SN is now by far the most prevalent. The broad banner of HIV-SN covers two aetiologically distinct, but clinically indistinguishable entities, originally called AIDS-Associated Sensory Neuropathy and ARV Toxic Neuropathy. However, since there are now clear data from a number of regions demonstrating that the incidence of HIV-SN has not decreased as less neurotoxic ARV drugs have been introduced, perhaps the importance of ARV Toxic Neuropathy in contributing to the clinical picture of HIV-SN may have been overestimated. The usual clinical presentation of HIV-SN is of a painful distal symmetrical sensory polyneuropathy characterised by a “die back” pattern of axonal degeneration, mainly of small fibres.

The lecture will commence with a brief summary of what is known about the prevalence of, risk factors for and clinical presentation of HIV-SN. This will be followed by a meta-analysis of analgesic clinical trials for HIV-SN, revealing an area of therapeutic need. Drugs that are effective for other forms of peripheral neuropathic pain, such as amitriptyline, gabapentin and pregabalin are not effective for pain relief in HIV-SN, although pregabalin does have efficacy for a subset of patients characterised by a pin prick hyperalgesia sensory profile. Cannabis is efficacious, although the barriers to this approach, particularly that of long term psychosis risk and legality preclude this as a routine therapy. Although the initial clinical trial of topical 8% capsaicin for HIV-SN indicated efficacy, this is now counterbalanced by a more recent study in which efficacy was not demonstrated. Surprisingly, despite their widespread use and guidelines promoting their use, opioids have not been adequately assessed for analgesic therapy in HIV-SN. The discussion will then move to what we have learned about the pathophysiology of HIV-SN from animal models. In particular, the role of the HIV glycoprotein GP120 will be discussed: although it was originally hypothesised that this was due to a direct interaction between GP120 and sensory neurones involving CCR5 and/or CxCR4 chemokine receptors, it is now apparent that an indirect GP120 driven processes via macrophages, Schwann cells and/or other non-neuronal intermediary cells predominates. The release of neurotoxic cytokines, such as TNF-α , appears to be a key intermediary step in GP120-induced axonal degeneration. Finally, identification of novel analgesic targets using gene microarrays of dorsal root ganglia harvested from animal models of HIV-SN will be briefly described.

  1. Funding: Wellcome Trust (London Pain Consortium), Innovative Medicines Initiative – EUROPAIN (European Commission and selected EFPIA members) and Derek Butler Trust.

Recommended reading

[1] Wallace VCJ, et al. Characterisation of rodent models of HIV-gp120 and antiretroviral associated neuropathic pain. Brain 2007;130:2688-702.Search in Google Scholar

[2] Wallace VCJ, et al. Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy. Pain 2007;133:47-63.Search in Google Scholar

[3] Maratou K, et al. Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain. European Journal of Pain 2009;13:398.Search in Google Scholar

[4] Phillips TJC, et al. Painful HIV-associated sensory neuropathy. Pain: Clinical Updates 2010;XVIII:1-8.Search in Google Scholar

[5] Phillips TJC, et al. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS ONE 2010;5:e14433.Search in Google Scholar
Published Online: 2012-07-01
Published in Print: 2012-07-01

© 2012 Scandinavian Association for the Study of Pain

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https://doi.org/10.1016/j.sjpain.2012.05.013

Articles in the same Issue

  1. Editorial comment
  2. Spontaneous pain is reduced by conditioning pain modulation in peripheral neuropathy but not in fibromyalgia—Implications for different pain mechanisms
  3. Clinical pain research
  4. Differential pain modulation in patients with peripheral neuropathic pain and fibromyalgia
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  10. Phantom pains and sensations – how does it feel? Only the patient really knows
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  13. Editorial comment
  14. Impact of mental stressor on conditioned pain modulation
  15. Original experimental
  16. The effect of a mental stressor on conditioned pain modulation in healthy subjects
  17. Editorial comment
  18. Pharmacological modulation of chronic pain after whiplash injury
  19. Clinical pain research
  20. Whiplash Associated Disorders (WAD): Responses to pharmacological challenges and psychometric tests
  21. Editorial comment
  22. Why are autonomic responses to pressure pain different from those to heat pain and ischaemic pain?
  23. Original experimental
  24. Cardiovascular responses to and modulation of pressure pain sensitivity in normotensive, pain-free women
  25. Correspondence
  26. Piriformis muscle injection guided by sciatic nerve stimulation: Quick, simple, and safe technique
  27. Correspondence
  28. Musculus piriformis syndrome: Localization and injection therapy—Comment to letter from Mayo-Moldes M et al. [1]
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  30. The “pain matrix” reloaded
  31. Abstracts
  32. Endpoints in animal pain models
  33. Abstracts
  34. Evaluating pain-related behavior in spinal cord injury
  35. Abstracts
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  37. Abstracts
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  39. Abstracts
  40. Human experimental models of central sensitization—Do they bridge the gap between animal models and clinical observations?
  41. Abstracts
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  45. Abstracts
  46. Chronic headaches–Goals and obstacles
  47. Abstracts
  48. Trigeminal neuralgia and other cranial neuralgias
  49. Abstracts
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  59. Abstracts
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  61. Abstracts
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  87. Abstracts
  88. The effect of tail-docking neonate piglets on ATF-3 and NR2B immunoreactivity in coccygeal dorsal root ganglia and spinal cord dorsal horn neurons: Preliminary data
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  90. Na+/K+-ATPase dependent regulation of astrocyte Ca2+ signalling: A novel mechanism for modulation of long-term pain?
  91. Abstracts
  92. Glutamate attenuates nitric oxide release from isolated trigeminal ganglion satellite glial cells
  93. Abstracts
  94. Acute behavioural responses to tail docking in piglets – Effects of increasing docking length?
  95. Abstracts
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  97. Abstracts
  98. Translational aspects of rectal evoked potentials: A comparative study in rats and humans
  99. Abstracts
  100. Time-course of analgesic effects of botulinum neurotoxin type A (BoNTA) on human experimental model of pain induced by injection of glutamate into temporalis muscle
  101. Abstracts
  102. The effect of nerve compression and capsaicin on contact heat evoked potentials (CHEPs) related to Aδ and C fibers
  103. Abstracts
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  109. Abstracts
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  111. Abstracts
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  116. Exercise and conditioned pain modulation have different effects on cuff pressure pain tolerance in humans
  117. Abstracts
  118. Hyperalgesia in human skin and deep-tissues inside and outside of a UVB irradiated area
  119. Abstracts
  120. Effect of experimental jaw muscle pain on bite force during mastication
  121. Abstracts
  122. Reflex threshold assessment methodology for evaluation of central sensitisation is vulnerable to EMG crosstalk
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  135. Abstracts
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  137. Abstracts
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  143. Abstracts
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  145. Abstracts
  146. Chronic pain after breast augmentation is associated with both signs of peripheral nerve injury and central nervous mechanisms
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  151. Abstracts
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  153. Abstracts
  154. Treatment with topical capsaicin: Experience from a pain clinic
  155. Abstracts
  156. Distribution of concussion related symptoms after whiplash injury in risk strata
  157. Abstracts
  158. HIV/AIDS in different cultures
  159. Abstracts
  160. Pain perception is altered in patients with medication-overuse headache but can improve after detoxification
  161. Abstracts
  162. Detoxification in a structured programme is effective for medication-overuse headache
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