Laurent F Martin
- Assistant Professor, Anesthesiology
- Member of the Graduate Faculty
Contact
- (520) 626-0611
- Arizona Health Sciences Center, Rm. 4441
- Tucson, AZ 85724
- laurentmartin@arizona.edu
Bio
No activities entered.
Interests
No activities entered.
Courses
2023-24 Courses
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Neuropharmacolgy
PHCL 553 (Spring 2024)
2022-23 Courses
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Neuropharmacolgy
PHCL 553 (Spring 2023) -
Independent Study
PSIO 399 (Fall 2022)
2021-22 Courses
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Neuropharmacolgy
PHCL 553 (Spring 2022)
Scholarly Contributions
Journals/Publications
- Martin, L. F., Ibrahim, M. M., Cheng, K., Washington, S. M., Denton, M., Goel, V., Khandekar, M., Largent-Milnes, T. M., & Patwardhan, A. (2023). Green light exposure elicits anti-inflammation, endogenous opioid release and dampens synaptic potentiation to relieve post-surgical pain. The Journal of Pain, 24, 509-529. doi:10.1016/j.jpain.2022.10.011
- Ibrahim, M. M., Martin, L. F., Patwardhan, A., Stratton, H. J., Flowers, M. E., Washington, S. M., Cheng, K., & Korah, H. E. (2022). Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies. Journal of Visualized Experiments. doi:10.3791/64555More infoManagement of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.
- Ibrahim, M. M., Patwardhan, A., Martin, L. F., Cheng, K., & Calligaro, H. (2022). Case Report: Green Light Exposure Relieves Chronic Headache Pain in a Colorblind Patient. Clinical Medicine Insights: Case Reports, 15, 117954762211251. doi:10.1177/11795476221125164
- Martin, L. F. (2022).
Targeting the vascular endothelial growth factor A/neuropilin 1 axis for relief of neuropathic pain
. Pain, 164(7), 1473-1488. doi:10.1097/j.pain.0000000000002850 - Patwardhan, A., Martin, L. F., Ramiro, I. B., Bjørn-Yoshimoto, W. E., Imperial, J. S., Gajewiak, J., Salcedo, P. F., Watkins, M., Taylor, D., Resager, W., Ueberheide, B., Bräuner-Osborne, H., Whitby, F. G., Hill, C. P., Concepcion, G. P., Olivera, B. M., & Safavi-Hemami, H. (2022). Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads. Science Advances, 8(12). doi:10.1126/sciadv.abk1410
- Cheng, K., Martin, L. F., Slepian, M. J., Patwardhan, A. M., & Ibrahim, M. M. (2021). Mechanisms and Pathways of Pain Photobiomodulation: A Narrative Review. The journal of pain, 22(7), 763-777.More infoA growing body of evidence supports the modulation of pain by light exposure. As such, phototherapy is being increasingly utilized for the management of a variety of pain conditions. The modes of delivery, and hence applications of phototherapy, vary by wavelength, intensity, and route of exposure. As such, differing mechanisms of action exist depending upon those parameters. Cutaneous application of red light (660 nm) has been shown to reduce pain in neuropathies and complex regional pain syndrome-I, whereas visual application of the same wavelength of red light has been reported to exacerbate migraine headache in patients and lead to the development of functional pain in animal models. Interestingly visual exposure to green light can result in reduction in pain in variety of pain conditions such as migraine and fibromyalgia. Cutaneous application typically requires exposure on the order of minutes, whereas visual application requires exposure on the order of hours. Both routes of exposure elicit changes centrally in the brainstem and spinal cord, and peripherally in the dorsal root ganglia and nociceptors. The mechanisms of photobiomodulation of pain presented in this review provide a foundation in furtherance of exploration of the utility of phototherapy as a tool in the management of pain. PERSPECTIVE: This review synopsizes the pathways and mechanisms through which light modulates pain and the therapeutic utility of different colors and exposure modalities of light on pain. Recent advances in photobiomodulation provide a foundation for understanding this novel treatment for pain on which future translational and clinical studies can build upon.
- Martin, L. F., Moutal, A., Cheng, K., Washington, S. M., Calligaro, H., Goel, V., Kranz, T., Largent-Milnes, T. M., Khanna, R., Patwardhan, A., & Ibrahim, M. M. (2021). Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation. The journal of pain, 22(12), 1646-1656.More infoBenefits of phototherapy were characterized in multiple diseases including depression, circadian rhythm disruptions, and neurodegeneration. Studies on migraine and fibromyalgia patients revealed that green light-emitting diodes (GLED) exposure provides a pragmatic and safe therapy to manage chronic pain. In rodents, GLED reversed hypersensitivity related to neuropathic pain. However, little is known about the underlying mechanisms of GLED efficacy. Here, we sought to understand how green light modulates the endogenous opioid system. We first characterized how exposure to GLED stimulates release of β-endorphin and proenkephalin in the central nervous system of male rats. Moreover, by individually editing each of the receptors, we found that µ- and δ-opioid receptors are required for green light's antinociceptive effect in naïve rats and a model of HIV-induced peripheral neuropathy. We investigated how GLED could increase pain thresholds, and explored its potential in reversing hypersensitivity in a model of HIV-related neuropathy. Through behavioral and gene editing approaches, we identified that green light provides antinociception via modulation of the endogenous opioid system in the spinal cord. This work identifies a previously unknown mechanism by which GLED can improve pain management. Clinical translation of these results will advance the development of an innovative therapy devoid of adverse effects. PERSPECTIVE: Development of new pain management therapies, especially for HIV patients, is crucial as long-term opioid prescription is not recommended due to adverse side effects. Green light addresses this necessity. Characterizing the underlying mechanisms of this potentially groundbreaking and safe antinociceptive therapy will advance its clinical translation.
- Martin, L., Bouvet, P., Chounlamountri, N., Watrin, C., Besançon, R., Pinatel, D., Meyronet, D., Honnorat, J., Buisson, A., Salin, P. A., & Meissirel, C. (2021). VEGF counteracts amyloid-β-induced synaptic dysfunction. Cell reports, 35(6), 109121.More infoThe vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aβo). Here, we show that VEGF accumulates in and around Aβ plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aβo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Notably, we demonstrate that VEGF gain of function rescues basal synaptic transmission, long-term potentiation (LTP), and dendritic spine alterations, and blocks long-term depression (LTD) facilitation triggered by Aβo. We further decipher underlying mechanisms and find that VEGF inhibits the caspase-3-calcineurin pathway responsible for postsynaptic glutamate receptor loss due to Aβo. These findings provide evidence for alterations of the VEGF pathway in AD models and suggest that restoring VEGF action on neurons may rescue synaptic dysfunction in AD.
- Martin, L., Ibrahim, M., Gomez, K., Yu, J., Cai, S., Chew, L. A., Bellampalli, S. S., Moutal, A., Largent-Milnes, T., Porreca, F., Khanna, R., Olivera, B. M., & Patwardhan, A. (2021). Conotoxin contulakin-G engages a neurotensin receptor 2 /R-type calcium channel (Cav2.3) pathway to mediate spinal antinociception. Pain.More infoIntrathecal application of contulakin-G (CGX), a conotoxin peptide and a neurotensin analogue, has been demonstrated to be safe and potentially analgesic in humans. However, the mechanism of action for CGX analgesia is unknown. We hypothesized that spinal application of CGX produces antinociception through activation of the presynaptic neurotensin receptor (NTSR)2. In this study, we assessed the mechanisms of CGX antinociception in rodent models of inflammatory and neuropathic pain. Intrathecal administration of CGX, dose dependently, inhibited thermal and mechanical hypersensitivities in rodents of both sexes. Pharmacological and clustered regularly interspaced short palindromic repeats/Cas9 editing of NTSR2 reversed CGX-induced antinociception without affecting morphine analgesia. Electrophysiological and gene editing approaches demonstrated that CGX inhibition was dependent on the R-type voltage-gated calcium channel (Cav2.3) in sensory neurons. Anatomical studies demonstrated coexpression of NTSR2 and Cav2.3 in dorsal root ganglion neurons. Finally, synaptic fractionation and slice electrophysiology recordings confirmed a predominantly presynaptic effect. Together, these data reveal a nonopioid pathway engaged by a human-tested drug to produce antinociception.
- Jain, S., Porreca, F., Martin, L., Mata, E. I., Salloum, M., Goel, V., Gunnala, P., Killgore, W. D., Jones-MacFarland, F. N., Khanna, R., Patwardhan, A., & Ibrahim, M. M. (2020). Green Light Exposure Improves Pain and Quality of Life in Fibromyalgia Patients: A Preliminary One-Way Crossover Clinical Trial. Pain Medicine, 22(1), 118-130. doi:10.1093/pm/pnaa329
- Martin, L. F. (2020).
SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia
. Pain, 162(1), 243-252. doi:10.1097/j.pain.0000000000002097 - Porreca, F., Killgore, W. D., Patwardhan, A. M., Martin, L. F., Jain, S. V., Salloum, M. M., Freeman, J., Khanna, R., Gannala, P., Goel, V., Jones-MacFarland, F. N., & Ibrahim, M. M. (2020). Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial. Cephalalgia, 41(2), 135-147. doi:10.1177/0333102420956711
- Benon, A., Ya, C., Martin, L., Watrin, C., Chounlamountri, N., Jaaoini, I., Honnorat, J., Pellier-Monnin, V., & Noraz, N. (2017). The Syk kinases orchestrate cerebellar granule cell tangential migration. Neuroscience, 360, 230-239.More infoThe tyrosine kinases of the Syk family are essential components of the well-characterized immunoreceptor ITAM-based signaling pathway. However, ITAM-based signaling typically does not function in isolation. Instead, it is enmeshed in the molecular network controlling cellular adhesion and chemotaxis. Consistent with the increasing number of data involving ITAM-bearing molecules in neuronal functions, we previously depicted a role for Syk kinases in the establishment of neuronal connectivity. In the developing cerebellum, we found that Syk is essentially expressed in the granule cells (GC) and more importantly, phosphorylated on tyrosine residues representative of an active form of the kinase in tangentially migrating GC. In light of these findings, experiments were performed to establish the implication of Syk in this process. We showed that Syk state of phosphorylation is spatiotemporally regulated during GC ontogeny. Moreover, the analysis of external granular layer microexplants treated with a Syk pharmacological inhibitor together with the quantification of ectopic GC in Syk; ZAP-70 mutant mice brought evidence of a requirement of Syk in GC tangential migration. Syk phosphorylation was induced by EphB2 engagement and locally turned down by a not yet identified factor that could in part explain the restricted pattern of Syk phosphorylation observed along GC migratory route. Whereas Syk kinase activity appeared not essential for ephrin/Eph-mediated axon extension, it might provide polarization signals required for proper nucleus translocation during GC migration. In conclusion, Syk kinase acts downstream of receptors controlling GC tangential migration.
- De Rossi, P., Harde, E., Dupuis, J. P., Martin, L., Chounlamountri, N., Bardin, M., Watrin, C., Benetollo, C., Pernet-Gallay, K., Luhmann, H. J., Honnorat, J., Malleret, G., Groc, L., Acker-Palmer, A., Salin, P. A., & Meissirel, C. (2016). A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior. Molecular psychiatry, 21(12), 1768-1780.More infoVascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic transmission and plasticity. VEGF increases the postsynaptic responses mediated by the N-methyl-D-aspartate type of glutamate receptors (GluNRs) in hippocampal neurons. This is concurrent with the formation of new synapses and with the synaptic recruitment of GluNR expressing the GluN2B subunit (GluNR-2B). VEGF induces a rapid redistribution of GluNR-2B at synaptic sites by increasing the surface dynamics of these receptors within the membrane. Consistently, silencing the expression of the VEGF receptor 2 (VEGFR2) in neural cells impairs hippocampal-dependent synaptic plasticity and consolidation of emotional memory. These findings demonstrated the direct implication of VEGF signaling in neurons via VEGFR2 in proper synaptic function. They highlight the potential of VEGF as a key regulator of GluNR synaptic function and suggest a role for VEGF in new therapeutic approaches targeting GluNR in depression.
- De Rossi, P., Harde, E., Dupuis, J. P., Martin, L., Chounlamountri, N., Bardin, M., Watrin, C., Benetollo, C., Pernet-Gallay, K., Luhmann, H. J., Honnorat, J., Malleret, G., Groc, L., Acker-Palmer, A., Salin, P. A., & Meissirel, C. (2016). Co-activation of VEGF and NMDA receptors promotes synaptic targeting of AMPA receptors. Molecular psychiatry, 21(12), 1647.