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Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution
Donovan LJ, Bridges CM, Nippert AR, Wang M, Wu S, Forman TE, Haight ES, Huck NA, Bond SF, Jordan CE, Gardner AM, Nair RV, Tawfik VL (2024) Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution. Cell Rep 43(2):113683. doi: 10.1016/j.celrep.2024.113683 PMID: 38261512
Objective: To study the role of microglia in pain resolution and determine if repopulated microglia actively resolve pain or initiate the transition from acute to chronic pain.
Summary: Pain resolution coincides with microglial repopulation in the spinal cord rather than depletion. Repopulated microglia exhibit unique gene expressions related to phagocytosis and stress response in mice. The study identified potential targets for developing microglial-targeted pain therapeutics by comparing mouse and human spinal cord microglial datasets.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
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Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation
Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415
Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).
Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.
Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Maintenance mechanism of nociplastic pain in males
McDonough KE (2022) Maintenance mechanism of nociplastic pain in males. University of Texas Medical Branch Thesis.
Objective: The objective of this dissertation is to elucidate the sex-specific mechanisms underlying the transition to and maintenance of a nociplastic pain state using animal models.
Summary: This PhD dissertation investigates the mechanisms underlying the transition from acute to chronic nociplastic pain using murine models. The study finds that in males, spinal microglial activation driven by GABAergic disinhibition allows normally innocuous stimulation to induce a transition to nociplastic pain maintained by spinal microglia and proinflammatory cytokines.
Usage: Intrathecal injection of Saporin or Mac-1-SAP at 8.85 μM.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Female-specific mechanisms of nociplastic pain in murine model
Hankerd K (2021) Female-specific mechanisms of nociplastic pain in murine model. The University of Texas Medical Branch at Galveston, Dept Neuroscience Thesis.
Objective: To study nociplastic pain the authors developed a murine model in which postinjury thermal stimulation of injured area triggers the transition to a nociplastic pain state more readily in females.
Summary: Postinjury stimulation of an injured area triggers the transition from transient pain to nociplastic pain, females are more susceptible to this transition, and allyl isothiocyanate -sensitive afferents at the previously injured area maintain the nociplastic pain state in a female gonadal hormone-dependent manner.
Usage: Intrathecal injection of Mac-1-SAP (IT-06) 8.85 mM in mice.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction
Li Y, Bao Y, Zheng H, Qin Y, Hua B (2021) Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction. Biomed Pharmacother 139:111653. doi: 10.1016/j.biopha.2021.111653
Summary: In this review the authors discuss the important role Src protein tyrosine kinase plays in the adverse consequences of clinical application of opioids
Usage: Intrathecal injection of Mac-1-SAP depletes microglial cells in the spinal dorsal horn and alleviates the loss of anti-nociception of morphine and prevents the decrease in morphine potency. This demonstrates that spinal microglial cells are necessary for morphine tolerance (15 µg; Leduc-Pessah et al., 2017).
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage
Li T, Zhao J, Xie W, Yuan W, Guo J, Pang S, Gan WB, Gómez-Nicola D, Zhang S (2021) Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage. J Neuroinflammation 18(1):81. doi: 10.1186/s12974-021-02127-w
Summary: The role of activated microglia during the development of ischemia remains controversial. The authors investigate the function of reactive microglia in the early stage of ischemic stroke. The results showed that specific depletion of microglia resulted in a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke.
Usage: Mac-1-SAP is used to specifically eliminate microglia. Hippocampal slices from mouse were incubated with 13-nM Mac-1-SAP for 3 to 7 days.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain
Andriessen AS, Donnelly CR, Ji RR (2021) Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain. Pain Rep 6(1):e867. doi: 10.1097/PR9.0000000000000867
Summary: Current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. The authors discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain.
Usage: Microglial ablation using Mac-1-SAP (15 μg in 8.8 μl i.t.) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl), is sufficient to attenuate nerve injury-induced pain in male, but not female mice.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Neuroimmune interactions and osteoarthritis pain: focus on macrophages
Geraghty T, Winter DR, Miller RJ, Miller RE, Malfait AM (2021) Neuroimmune interactions and osteoarthritis pain: focus on macrophages. Pain Rep 6(1):e892. doi: 10.1097/PR9.0000000000000892
Summary: The contribution of macrophages to osteoarthritis (OA) joint damage has garnered much attention in recent years. The authors discuss how macrophages participate in the initiation and maintenance of pain in OA and provide a review of preclinical models of OA.
Usage: Using the rat monoiodoacetate-induced (MIA) model of advanced knee OA, increased microglia were observed in the ipsilateral and contralateral dorsal horn by day 7; specific ablation of spinal microglia through intrathecal injections of Mac-1-SAP (15 mcg per intrathecal injection on days 0, 1, and 2), attenuated mechanical allodynia by days 5 and 7 after MIA.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Inflammatory macrophages facilitate mechanical stress-induced osteogenesis.
Zhang F, Huan L, Xu T, Li G, Zheng B, Zhao H, Guo Y, Shi J, Sun J, Chen A (2020) Inflammatory macrophages facilitate mechanical stress-induced osteogenesis. Aging (Albany NY) 12(4):3617-3625. doi: 10.18632/aging.102833
Summary: In a mouse model of distraction osteogenesis (DO), there was significant increase in macrophages in the regeneration area. This suggests that targeting inflammatory macrophages may help to improve clinical bone repair.
Usage: For saporin-mediated depletion of macrophages, DO-surgery-treated mice received an intraventricular (iv) injection of either Mac-1-SAP or Rat IgG-SAP (20µg) once every 3 days.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Rat IgG-SAP (Cat. #IT-17)
Systems pathology of neuropathic pain and fibromyalgia.
Ueda H (2019) Systems pathology of neuropathic pain and fibromyalgia. Biol Pharm Bull 42(11):1773-1782. doi: 10.1248/bpb.b19-00535
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)