Chronic opioid therapy and opioid tolerance: a new hypothesis.
Abstract
Opioids are efficacious and cost-effective analgesics, but tolerance limits their
effectiveness. This paper does not present any new clinical or experimental data but
demonstrates that there exist ascending sensory pathways that contain few opioid receptors.
These pathways are located by brain PET scans and spinal cord autoradiography. These
nonopioid ascending pathways include portions of the ventral spinal thalamic tract
originating in Rexed layers VI-VIII, thalamocortical fibers that project to the primary
somatosensory cortex (S1), and possibly a midline dorsal column visceral pathway.
One hypothesis is that opioid tolerance and opioid-induced hyperalgesia may be caused
by homeostatic upregulation during opioid exposure of nonopioid-dependent ascending
pain pathways. Upregulation of sensory pathways is not a new concept and has been
demonstrated in individuals impaired with deafness or blindness. A second hypothesis
is that adjuvant nonopioid therapies may inhibit ascending nonopioid-dependent pathways
and support the clinical observations that monotherapy with opioids usually fails.
The uniqueness of opioid tolerance compared to tolerance associated with other central
nervous system medications and lack of tolerance from excess hormone production is
discussed. Experimental work that could prove or disprove the concepts as well as
flaws in the concepts is discussed.
Type
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https://hdl.handle.net/10161/10354Published Version (Please cite this version)
10.1155/2013/407504Publication Info
Goldberg, Joel S (2013). Chronic opioid therapy and opioid tolerance: a new hypothesis. Pain Res Treat, 2013. pp. 407504. 10.1155/2013/407504. Retrieved from https://hdl.handle.net/10161/10354.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Joel Steven Goldberg
Adjunct Professor in the Department of Anesthesiology

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