TIMP-1 Attenuates the Development of Inflammatory Pain Through MMP-Dependent and Receptor-Mediated Cell Signaling Mechanisms.

Unresolved inflammation is a significant predictor for developing chronic pain, and targeting the mechanisms underlying inflammation offers opportunities for therapeutic intervention. During inflammation, matrix metalloproteinase (MMP) activity contributes to tissue remodeling and inflammatory signaling, and is regulated by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 and -2 have known roles in pain, but only in the context of MMP inhibition.

Mechanisms Underlying Bone and Joint Pain.

Purpose Of Review: The goal of this review is to provide a broad overview of the current understanding of mechanisms underlying bone and joint pain.

Recent Findings: Bone or joint pathology is generally accompanied by local release of pro-inflammatory cytokines, growth factors, and neurotransmitters that activate and sensitize sensory nerves resulting in an amplified pain signal. Modulation of the pain signal within the spinal cord and brain that result in net increased facilitation is proposed to contribute to the development of chronic pain.

A Kappa Opioid Receptor Agonist Blocks Bone Cancer Pain Without Altering Bone Loss, Tumor Size, or Cancer Cell Proliferation in a Mouse Model of Cancer-Induced Bone Pain.

Unlabelled: Breast cancer metastasizes to bone, diminishing quality of life of patients because of pain, fracture, and limited mobility. Cancer-induced bone pain (CIBP) is characterized as moderate to severe ongoing pain, primarily managed by mu opioid agonists such as fentanyl. However, opioids are limited by escalating doses and serious side effects.

Mediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Rats.

Cancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia.

Effects of Treadmill Exercise on Advanced Osteoarthritis Pain in Rats.

Objective: Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating ongoing pain that is persistent, resistant to nonsteroidal antiinflammatory drugs (NSAIDs), and associated with advanced OA is unknown.

Methods: Rats treated with intraarticular (IA) monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days postinjection.

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

Unlabelled: Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood.