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Neuroscience

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Neuroscience

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Neuroscience

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Neuroscience

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Translational Science

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Abstract

Background: Chronic pain, especially neuropathic, is the most severe form of chronic pain. People with neuropathic pain often have hyperalgesia, allodynia, and ongoing pain. 53% of American adults living with Human immunodeficiency virus (HIV) are over the age of 50, due mainly to the successful treatment regimens helping HIV-positive adults survive for decades with HIV and reach age-related neurodegenerative diseases such as Alzheimer’s disease (AD). As the population ages, the number of individuals who experience AD and HIV-related neuropathic pain will also increase. Therefore, the comorbidity of these two clinically unmet needs will become an increasingly pressing challenge and unavoidable. While chronic pain is difficult to manage, the AD condition poses an additional challenge. It also requires analgesics without adverse effects on AD cognitive deficit. Additionally, a recent retrospective cohort study showed that gabapentin (the gold standard for neuropathic pain) was significantly associated with deleterious neurocognitive changes among those 65 years and older. This data raise major concerns about the use of gabapentin in people with AD whose cognitive functions are in progressive deterioration. Therefore, there is an urgent need foralternative analgesics when HIV-related neuropathic pain and AD are comorbid in old age. Better outcomes can be achieved by developing new and improved therapeutics or, more immediately, by identifying favorable compounds that are already available or emerging as potential new analgesics or analgesic adjuvants. α-pinene is a monoterpene and a food additive approved by the FDA. Its pharmacological profiles make it unique and suitable for pain and AD comorbidity. α-pinene is an AChEI that may aid AD memory. Preclinical data suggest an analgesic effect of α-pinene.

Methods: We will use the chimeric HIV (EcoHIV) model to mimic HIV related neuropathic pain. This model involves injecting conventional mice with EcoHIV, a virus that uses species-specific cellular receptors to enter mouse cells. The Novel Object Recognition Test (NOR) was performed in an open field box. NOR relies on rodents' natural proclivity for exploring novelty. Cold hypersensitivity is assessed using the acetone drop method. Mechanical allodynia was assessed using the digital electrovonfrey. Filament is applied with increasing force until a paw withdrawal response is elicited.

Results: Pinene reduced pain induced by EcoHIV in tau mice. It has no adverse effect on cognitive function. This is proven by both the Vonfrey and Acetone testing, along with the NOR test for cognitive function.

Conclusion: Pinene is effective in HIV neuropathic pain without affecting cognitive function in Alzheimer’s Disease. This can be implemented into future studies as we continue to learn more.

This work is supported by NIH grants (NS134408 and AG84378)

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HIV-related neuropathic pain and AD comorbidity: Effect of Pinene

Background: Chronic pain, especially neuropathic, is the most severe form of chronic pain. People with neuropathic pain often have hyperalgesia, allodynia, and ongoing pain. 53% of American adults living with Human immunodeficiency virus (HIV) are over the age of 50, due mainly to the successful treatment regimens helping HIV-positive adults survive for decades with HIV and reach age-related neurodegenerative diseases such as Alzheimer’s disease (AD). As the population ages, the number of individuals who experience AD and HIV-related neuropathic pain will also increase. Therefore, the comorbidity of these two clinically unmet needs will become an increasingly pressing challenge and unavoidable. While chronic pain is difficult to manage, the AD condition poses an additional challenge. It also requires analgesics without adverse effects on AD cognitive deficit. Additionally, a recent retrospective cohort study showed that gabapentin (the gold standard for neuropathic pain) was significantly associated with deleterious neurocognitive changes among those 65 years and older. This data raise major concerns about the use of gabapentin in people with AD whose cognitive functions are in progressive deterioration. Therefore, there is an urgent need foralternative analgesics when HIV-related neuropathic pain and AD are comorbid in old age. Better outcomes can be achieved by developing new and improved therapeutics or, more immediately, by identifying favorable compounds that are already available or emerging as potential new analgesics or analgesic adjuvants. α-pinene is a monoterpene and a food additive approved by the FDA. Its pharmacological profiles make it unique and suitable for pain and AD comorbidity. α-pinene is an AChEI that may aid AD memory. Preclinical data suggest an analgesic effect of α-pinene.

Methods: We will use the chimeric HIV (EcoHIV) model to mimic HIV related neuropathic pain. This model involves injecting conventional mice with EcoHIV, a virus that uses species-specific cellular receptors to enter mouse cells. The Novel Object Recognition Test (NOR) was performed in an open field box. NOR relies on rodents' natural proclivity for exploring novelty. Cold hypersensitivity is assessed using the acetone drop method. Mechanical allodynia was assessed using the digital electrovonfrey. Filament is applied with increasing force until a paw withdrawal response is elicited.

Results: Pinene reduced pain induced by EcoHIV in tau mice. It has no adverse effect on cognitive function. This is proven by both the Vonfrey and Acetone testing, along with the NOR test for cognitive function.

Conclusion: Pinene is effective in HIV neuropathic pain without affecting cognitive function in Alzheimer’s Disease. This can be implemented into future studies as we continue to learn more.

This work is supported by NIH grants (NS134408 and AG84378)

 

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