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)

See Also:

• Echeverry S et al. Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801, 2017.
• Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

Maiarù M, Leese C, Silva-Hucha S, Fontana-Giusti S, Tait L, Tamagnini F, Davletov B, Hunt SP (2024) Substance P-botulinum mediates long-term silencing of pain pathways that can be re-instated with a second injection of the construct in mice. J Pain 11 doi: 10.1016/j.jpain.2024.01.331 PMID: 38218509

Summary: The authors discuss how Substance P-Botulinum is used to try to replicate the permanent results achieved with Substance P-Saporin (SP-SAP, SSP-SAP).

Related Products: SSP-SAP (Cat. #IT-11)

See Also:

• Mantyh PW et al. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279, 1997.
• Nichols ML et al. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558-1561, 1999.
• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
• Wiley RG et al. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345, 2007.
• Vierck CJ et al. Comparison of operant escape and innate reflex responses to nociceptive skin temperatures produced by heat and cold stimulation of rats. Behav Neurosci. 2004;118(3):627-35.

Yaksh TL, dos Santo G, Lemes J, Malange K (2023) Neuraxial drug delivery in pain management: An overview of past, present, and future. Anaesthesiology doi: 10.1016/j.bpa.2023.04.003

Objective: Activation of neuraxial nociceptive linkages leads to a high level of encoding of the message that is transmitted to the brain and that can initiate a pain state with its attendant emotive covariates. The authors review the encoding of this message and describe the how it is subject to regulation by pharmacological targeting of dorsal root ganglion and dorsal horn systems.

Summary: Authors provide an overview of the past, present and future directions of the biology, pharmacology and technology relevant to the use of the neuraxial route. SP-SAP was used as a neuraxial toxin to eliminate NK1R expressing cells, which characteristic of neurons known to be the second order neurons responding to C fiber input. Delivery of SP-SAP results in long-lasting loss of NK1 bearing dorsal horn neurons and analgesia.

Related Products: SP-SAP (Cat. #IT-07)

Donertas-Ayaz B, Caudle RM (2023) Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities. Neurobiol Pain 13:100124. doi: 10.1016/j.ynpai.2023.100124 PMID: 36974102

Objective: To summarize the knowledge about the involvement of noradrenaline in acute and chronic trigeminal pain conditions and how the activity of the locus coeruleus (LC) noradrenergic neurons changes in response to acute and chronic pain conditions and how these changes might be involved in pain-related comorbidities including anxiety, depression, and sleep disturbance.

Summary: LC inhibition of nociceptive transmission in acute pain and in longterm neuropathic pain increases the tonic activity of LC-NA neurons. These changes may contribute to impaired descending pain modulation and pain-related comorbidities such as depression, anxiety, and sleep disorders.

Usage: Elimination of NA neurons via injection of anti-dopamine β-hydroxylase-saporin (Anti-DBH-SAP) into the lateral ventricle and trigeminal brainstem nuclei three weeks after infraorbital nerve injury attenuated mechanical allodynia

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Iqbal Z, Lei Z, Ramkrishnan AS, Liu S, Hasan M, Akter M, Lam YY, Li Y (2023) Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats. Commun Biol 6:10. doi: 10.1038/s42003-022-04405-6 PMID: 36604595

Objective: To identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC).

Summary: The findings suggest that projection-specific adrenergic astrocytic signaling in ACC is integral to system-wide neuromodulation in response to visceral stimuli and plays a key role in mediating pain-related aversion consolidation and memory formation.

Usage: 0.25 ug of Anti-DBH-SAP (1 μg/μl) was injected into each hemisphere of locus coeruleus (LC).

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Silva AR (2022) Uncovering central and peripheral pain mechanisms in Alzheimer’s disease. King’s College London Thesis.

Objective: To investigate alterations within the nociceptive pathways, under neuropathic pain conditions.

Summary: The data suggest a disrupted opioidergic tone in TASTPM mice, which followed by peripheral nerve injury, is mediated by peripheral immune cells.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

See Also:

• Brightwell JJ et al. Noradrenergic neurons in the locus coeruleus contribute to neuropathic pain. Neuroscience 160:174-185, 2009.

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)

Nguyen KL, Lamerand SR, Deshpande RP, Taylor BK (2021) Featured Article: Selective ablation of IB4+ primary afferent neurons reduces mechanical and cold hyperalgesia in an EAE mouse model of multiple sclerosis. Targeting Trends 22

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Nguyen KL et al. Contribution of small diameter non-peptidergic primary afferent neurons to central neuropathic pain in a new, more clinically relevant mouse model of multiple sclerosis. Neuroscience 2021 Abstracts P377/07, 2021. Society for Neuroscience, Virtual

Kohno K, Shirasaka R, Yoshihara K, Mikuriya S, Tanaka K, Takanami K, Inoue K, Sakamoto H, Ohkawa Y, Masuda T, Tsuda M (2022) A spinal microglia population involved in remitting and relapsing neuropathic pain. Science 376(6588):86-90. doi: 10.1126/science.abf6805

Objective: To investigate pain recovery mechanisms.

Summary: The authors reveal a mechanism for the remission and recurrence ofneuropathic pain, providing potential targets for therapeutic strategies.

Usage: The dose of CTB-SAP and IB4-SAP was 8 ug/10 uL, diluted in PBS.

Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10)

Yun-Fei L, Zhang J, Wang XQ, Peng JJ, Ling BF, Liu FT, Yang F, Dong G, Yu YQ (2022) Noradrenergic innervations of the medial prefrontal cortex mediate empathy for pain in rats via the α1 and β receptors. Behav Brain Res 10:113828. doi: 10.1016/j.bbr.2022.113828

Objective: To study the roles of the locus coeruleus (LC) to medial prefrontal cortex (mPFC) pathway in pain empathy in rats.

Summary: Results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and β receptors.

Usage: Noradrenergic innervations of the mPFC were selectively eliminated through intra-mPFC injections of Anti-DBH-SAP.

Related Products: Anti-DBH-SAP (Cat. #IT-03)