Articles: neuralgia.
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The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. ⋯ This effect was associated with a decline in the activity of primary afferent Aδ- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions.
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Opioids are widely prescribed for chronic pain, including neuropathic pain, despite growing evidence of long-term harm. Previous preclinical studies have documented exacerbation of nociceptive hypersensitivity, including that induced by peripheral nerve injury, by morphine. The present series of behavioral studies sought to replicate and extend our prior research, which demonstrated a multimonth exacerbation of nociceptive hypersensitivity by a 5-day course of morphine initiated 10 days after nerve injury. ⋯ Furthermore, enduring exacerbation of nociceptive hypersensitivity is also observed when the same dosing regimen for either morphine, fentanyl, or oxycodone begins 1 month after nerve injury. Finally, a striking result from these studies is that no such exacerbation of nociceptive hypersensitivity occurs when either morphine, fentanyl, or oxycodone dosing begins at the time of nerve injury. These results extend our previous findings that morphine exacerbates nociceptive hypersensitivity to the clinically relevant opioids fentanyl and oxycodone when administered after the development of nociceptive hypersensitivity, while also providing possible clinically relevant insight into when these opioids can be safely administered and not exacerbate neuropathic pain.