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Synthesis of diversely substituted pyridin-2(1)-ones and in vivo evaluation of their anti-allodynic effect on cutaneous inflammatory mechanical allodynia.

A series of 3,5-disubtituted pyridin-2(1)-ones was synthesized. As part of a structure-activity relationship study performed in this series, structural modifications were based on 3-(indol-4-yl)-5-(pyridin-4-ylamino)pyridin-2(1)-one B, which exhibited a potent anti-allodynic […]

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Evodiamine suppresses endometriosis development induced by early EBV exposure through inhibition of ERβ.

Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to persistent pelvic pain and may […]

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Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury.

Traumatic spinal cord injury (SCI) results in immediate tissue necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progressive hemorrhagic necrosis […]

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Human adipose and synovial-derived MSCs synergistically attenuate osteoarthritis by promoting chondrocyte autophagy through FoxO1 signaling.

Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human […]

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Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity.

Mechanosensitive PIEZO2 ion channels play roles in touch, proprioception, and inflammatory pain. Currently, there are no small molecule inhibitors that selectively inhibit PIEZO2 over PIEZO1. The TMEM120A protein was shown […]

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Parabrachial neurons promote nociplastic pain.

The parabrachial nucleus (PBN) in the dorsal pons responds to bodily threats and transmits alarm signals to the forebrain. Parabrachial neuron activity is enhanced during chronic pain, and inactivation of […]

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Unraveling the molecular reason of opposing effects of α-mangostin and norfluoxetine on TREK-2 at the same binding site [[EQUATION]].

TWIK-related K(+) channel (TREK)-2, expressed in sensory neurons, is involved in setting membrane potential, and its modulations contributes to the generation of nociceptive signals. Although acute and chronic pain is […]

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Mechanism of gabapentinoid potentiation of opioid effects on cyclic AMP signaling in neuropathic pain.

Over half of spinal cord injury (SCI) patients develop opioid-resistant chronic neuropathic pain. Safer alternatives to opioids for treatment of neuropathic pain are gabapentinoids (e.g., pregabalin and gabapentin). Clinically, gabapentinoids […]

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Preclinical Evaluation of Sigma 1 Receptor Antagonists as a Novel Treatment for Painful Diabetic Neuropathy.

The global prevalence of diabetes is steadily rising, with an estimated 537 million adults affected by diabetes in 2021, projected to reach 783 million by 2045. A severe consequence of […]

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Nanotechnology-Enhanced Naloxone and Alternative Treatments for Opioid Addiction.

Opioids are commonly prescribed to address intense, ongoing pain associated with cancer, as well as long-lasting noncancer-related pain when alternative methods have proven ineffective. Individuals who exhibit both chronic pain […]

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