Articles: hyperalgesia.
-
Expectancies for pain and pain relief are central to experimental models of placebo analgesia and nocebo hyperalgesia and are a promising target for clinical intervention in patients with chronic pain. Affective states may play an important role in modulating the degree to which expectancies influence pain, broadening the opportunities for intervention targets. However, findings to date have been mixed and mostly limited to laboratory designs. ⋯ Relatedly, higher morning positive affect predicted greater odds of experiencing a match between pain expectancies and pain experience when the expectation was for low, but not high, pain levels (odds ratio = 1.19, confidence interval: 1.01-1.41, P = 0.03). Negative affect, in contrast, did not significantly influence the assimilation of high pain expectancies with high pain experiences. These findings extend previous experimental studies by showing that the association of daily pain expectancies with pain experience varies as a function of affective state.
-
Mechanical allodynia impinges on the life quality of patients. Hen Egg Lysozyme (HEL) is a substance extracted from eggs that is commonly used to inhibit bacterial activity. The role of HEL in regulating and treating pain is unclear. ⋯ In addition, pre-given of HEL also significantly attenuates the static mechanical allodynia induced by overexpression of TACAN in mice, and the effect of HEL can be blocked by Parkin-siRNA. This indicates that HEL increases the expression of Parkin through epigenetic mechanisms and then decreases TACAN membrane trafficking in sensory neurons to relieve static mechanical hypersensitivity. Therefore, we reveal a novel function of HEL, which is a potential substance for the treatment of static mechanical pain.
-
The basal ganglia modulate somatosensory pain pathways, but it is unclear whether a common circuit exists to mitigate hyperalgesia in pain states induced by peripheral nociceptive stimuli. As a key output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) may be a candidate for this role. To test this possibility, we optogenetically modulated SNr GABAergic neurons and examined pain thresholds in freely behaving male mice in inflammatory and neuropathic pain states as well as comorbid depression in chronic pain. ⋯ However, SNr modulation did not affect baseline pain thresholds. We also found that SNr-STN GABAergic projection was attenuated in pain states, resulting in disinhibition of STN neurons. Thus, impairment of the SNr-STN GABAergic circuit may be a common pathophysiology for the maintenance of hyperalgesia in both inflammatory and neuropathic pain states and the comorbid depression in chronic pain; compensating this circuit has potential to effectively treat pain related conditions.
-
Transient receptor potential vanilloid-1 (TRPV1), activated by heat, acidic pH, endogenous vanilloids and capsaicin, is essential for thermal hyperalgesia. Under inflammatory conditions, phosphorylation of TRPV1 by protein kinase C (PKC) can sensitize the channel and decrease the activation threshold. Src kinase also phosphorylates TRPV1, promoting channel trafficking to the plasma membrane. These post-translational modifications are important for several chronic pain conditions. This study presents a previously undescribed relationship between Src and PKC phosphorylation of TRPV1, influencing the thermal hypersensitivity associated with TRPV1 activation. ⋯ Src kinase-mediated phosphorylation of TRPV1 is a critical regulator of the PKC-induced sensitization induced by multiple inflammatory mediators. This suggest a new regulatory mechanism governing TRPV1 function and a potential therapeutic target for inflammatory type pain, including cancer pain where Src antagonists are currently utilized.
-
Randomized Controlled Trial
Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II).
Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. ⋯ Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.