Multi-Electrode Array of Sensory Neurons as an In Vitro Platform to Identify the Nociceptive Response to Pharmaceutical Buffer Systems of Injectable Biologics.
Animals
Biological Products
/ administration & dosage
Buffers
Cells, Cultured
Drug Evaluation, Preclinical
/ instrumentation
Electrodes
Ganglia, Spinal
/ cytology
Injection Site Reaction
/ prevention & control
Injections
/ adverse effects
Nociception
/ drug effects
Pain
/ etiology
Primary Cell Culture
Rats
Sensory Receptor Cells
/ drug effects
buffer system
injection site pain
multi/micro electrode array
nociception
sensory neurons
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
22
03
2021
accepted:
14
06
2021
pubmed:
11
7
2021
medline:
21
12
2021
entrez:
10
7
2021
Statut:
ppublish
Résumé
Pharmaceutical buffer systems, especially for injectable biologics such as monoclonal antibodies, are an important component of successful FDA-approved medications. Clinical studies indicate that buffer components may be contributing factors for increased injection site pain. To determine the potential nociceptive effects of clinically relevant buffer systems, we developed an in vitro multi-electrode array (MEA) based recording system of rodent dorsal root ganglia (DRG) sensory neuron cell culture. This system monitors sensory neuron activity/firing as a surrogate of nociception when challenged with buffer components used in formulating monoclonal antibodies and other injectable biologics. We show that citrate salt and citrate mannitol buffer systems cause an increase in mean firing rate, burst frequency, and burst duration in DRG sensory neurons, unlike histidine or saline buffer systems at the same pH value. Lowering the concentration of citrate leads to a lower firing intensity of DRG sensory neurons. Increased activity/firing of DRG sensory neurons has been suggested as a key feature underlying nociception. Our results support the utility of an in vitro MEA assay with cultured DRG sensory neurons to probe the nociceptive potential of clinically relevant buffer components used in injectable biologics.
Identifiants
pubmed: 34244893
doi: 10.1007/s11095-021-03075-z
pii: 10.1007/s11095-021-03075-z
doi:
Substances chimiques
Biological Products
0
Buffers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1179-1186Subventions
Organisme : National Science Foundation: Graduate Research Fellowship
ID : DGE-1842166
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Birnie K, McGrath P, Chambers C. When does pain matter? Acknowledging the subjectivity of clinical significance. Pain. 2012;153(12):2311–4.
doi: 10.1016/j.pain.2012.07.033
Aronson R. The role of comfort and discomfort in insulin therapy. Diabetes Technol Ther. 2012;14(8):741–7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409452/ .
doi: 10.1089/dia.2012.0038
Taddio A, Chambers CT, Halperin SA, Ipp M, Lockett D, Rieder MJ, et al. Inadequate pain management during routine childhood immunizations: the nerve of it. Clin Ther. 2009;31(S2):S152–67 https://www.ncbi.nlm.nih.gov/pubmed/19781434/ .
doi: 10.1016/j.clinthera.2009.07.022
Taddio A, Ipp M, Thivakaran S, Jamal A, Parikh C, Smart S, et al. Survey of the prevalence of immunization non-compliance due to needle fears in children and adults. Vaccine. 2012;30(32):4807–12 https://www.ncbi.nlm.nih.gov/pubmed/22617633/ .
doi: 10.1016/j.vaccine.2012.05.011
McMurtry CM, Noel M, Taddio A, Antony MM, Asmundson GJ, Riddell RP, et al. Interventions for individuals with high levels of needle fear: systematic review of randomized controlled trials and quasi-randomized controlled trials. Clin J Pain. 2015;31(Suppl 10):S109–23.
doi: 10.1097/AJP.0000000000000273
Baxter AL, Cohen LL, Burton M, Mohammed A, Lawson ML. The number of injected same-day preschool vaccines relates to preadolescent needle fear and HPV uptake. Vaccine. 2017;35(33):4213–9.
doi: 10.1016/j.vaccine.2017.06.029
Usach I, Martinez R, Festini T, Peris JE. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36:2986–96.
doi: 10.1007/s12325-019-01101-6
Kaplon H, Reichert JM. Antibodies to watch in 2019. mAbs. 2018;11(2):219–38. https://doi.org/10.1080/19420862.2018.1556465 .
doi: 10.1080/19420862.2018.1556465
pubmed: 30516432
pmcid: 6380461
Srivastava A, Brophy G, Agarkhed M. Approaches to alleviating subcutaneous injection-site pain for citrate formulations. Pharm Tech. 2020:32–7.
Broadhead J, Gibson M. Pharmaceutical pre-formulation and formulation. Informa Healthcare. 2009:325–47.
NHS (6 July 2019) Regional medicines optimization committee briefing, best value biologicals: adalimumab update. https://www.sps.nhs.uk/wp-content/uploads/2019/07/Adalimumab-RMOC-Briefing-6.pdf
Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in Normal and nerve injured rats. Pain. 1983;17(4):321–39 https://www.ncbi.nlm.nih.gov/pubmed/6664680 .
doi: 10.1016/0304-3959(83)90164-1
Yang Y, Mis MA, Estacion M, Dib-Hajj SD, Waxman SG. NaV1.7 as a pharmacogenomic target for pain: moving toward precision medicine. Trends Pharmacol Sci. 2018;39(3):258–75.
doi: 10.1016/j.tips.2017.11.010
Spira ME, Avaid H. Multi-electrode array technologies for neuroscience and cardiology. Nature Nanotech. 2013;8:83–94.
doi: 10.1038/nnano.2012.265
Verma P, Eaton M, Kienle A, Flockerzi D, Yang Y, Ramkrishna D. Examining sodium and potassium channel conductances involved in hyperexcitability of chemotherapy-induced peripheral neuropathy: a mathematical and cell culture-based study. Front Comp Neurosci. 2020;14:564980. https://doi.org/10.3389/fncom.2020.564980 .
doi: 10.3389/fncom.2020.564980
Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, et al. Nav1.7-A1632G mutation from a family with inherited erythromelalgia: enhanced firing of dorsal root ganglia neurons evoked by thermal stimuli. J Neurosci. 2016;36(28):7511–22.
doi: 10.1523/JNEUROSCI.0462-16.2016
Yang Y, Adi T, Effraim PR, Chen L, Dib-Hajj SD, Waxman SG. Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Nav 1.7 mutation I234T. Br J Pharmacol. 2018;175:2261–71.
Moy JK, Khoutorsky A, Asideu MN, Black BJ, Kuhn JL, Barragan-Iglesias P, et al. The MNK–eIF4E signaling axis contributes to injury-induced nociceptive plasticity and the development of chronic pain. J Neurosci. 2017;37(31).
Black BJ, Atmaramani R, Pancrazio JJ. Spontaneous and evoked activity from murine ventral horn cultures on microelectrode arrays. Front Cell Neurosci. 2017;11:304.
doi: 10.3389/fncel.2017.00304
Pancrazio JJ, Keefer EW, Ma W, Stenger DA, Gross GW. Neurophysiologic effects of chemical agent hydrolysis products on cortical neurons in vitro. Neurotox. 2001;22(3):393–400.
doi: 10.1016/S0161-813X(01)00028-6
Atmaramani RR, Black BJ, Bryan de la Pena J, Campbell ZT, Pancrazio JJ Conserved expression of Nav1.7 and Nav1.8 contribute to the spontaneous and thermally evoked excitability in IL-6 and NGF-Sensitized adult dorsal root ganglion neurons in vitro. Bioengineering. 2020;7(44).
Whitaker N, Xiong J, Samantha EP, Kumar V, Middaugh CR, Joshi SB, et al. A formulation development approach to identify and select stable ultra-high-concentration monoclonal antibody formulations with reduced viscosities. J Pharm Sci. 2017;106:3210–41. https://doi.org/10.1016/j.xphs.2017.06.017 .
doi: 10.1016/j.xphs.2017.06.017
Kamarzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Delivery Reviews. 2011;63:1118–59. https://doi.org/10.1016/j.addr.2011.07.006 .
doi: 10.1016/j.addr.2011.07.006
Mis MA, Yang Y, Tanaka BS, Gomis-Perez C, Liu S, Dib-Hajj F, et al. Resilience to pain: a peripheral component identified using induced pluripotent stem cells and dynamic clamp. J Neurosci. 2019;39(3):382–92.
doi: 10.1523/JNEUROSCI.2433-18.2018
Laursen T, Hansen B, Fisker S. Pain perceptions after subcutaneous injections of media containing different buffers. Basic and Clinical Pharm and Tox. 2006;98:218–21.
doi: 10.1111/j.1742-7843.2006.pto_271.x
Shi GH, Pisupati K, Parker JG, Covarti VJ, Payne CD, Xu W, et al. De Felippis MR subcutaneous injection site pain of formulation matrices. Pharm Res. 2021;38:779–93.
doi: 10.1007/s11095-021-03047-3
Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010;120(11):3760–72. https://doi.org/10.1172/JCI42843 .
doi: 10.1172/JCI42843
pubmed: 21041958
pmcid: 2964977
Amir R, Michaelis M, Devor M. Burst discharge in primary sensory neurons: triggered by subthreshold oscillations. Maintained by Depolarizing Afterpotentials. J Neurosci. 2002;22(3):1187–98.
Newberry K, Wang S, Hoque N, Kiss L, Ahlijanian MK, Herrington J, et al. Development of a spontaneously active dorsal root ganglia assay using multiwell multielectrode arrays. J Neurophysiol. 2016;115(6):3217–28. https://doi.org/10.1152/jn.01122.2015 .
doi: 10.1152/jn.01122.2015
pubmed: 27052585
pmcid: 4946598
Frenken LA, van Lier HJ, Jordans JG, Leunissen KM, van Leusen R, Verstappen VM, et al. Identification of the component part in an epoetin alfa preparation that causes pain after subcutaneous injection. Am J Kidney Dis. 1993;22(4):553–6. https://doi.org/10.1016/s0272-6386(12)80928-0 .
doi: 10.1016/s0272-6386(12)80928-0
pubmed: 8213795
Kappelgaard AM, Bojesen A, Skysgaard K, Sjogren I, Laursen T. Liquid growth hormone: preservatives and buffers. Horm Res. 2004;62(3):98–103 https://www.ncbi.nlm.nih.gov/pubmed/15539807 .
pubmed: 15539807
Bertrand H, Kyriazia M, Reeves KD, Lyftogt J, Rabago D. Topical mannitol reduces capsaicin-induced pain: results of a pilot-level, double-blind, randomized controlled trial. J Injury, Function, and Rehab. 2015;7(11).
Lee SK, Yang DS, Lee JW, Choy WS. Four treatment strategies for complex regional pain syndrome type 1. Orthopedics. 2012;35(6):e834–42.
pubmed: 22691654
Tan ECTH, Tacken MCT, Groenewound JMM, van Goor H, Frolke JPM. Mannitol as salvage treatment for complex regional pain syndrome type I. Injury. 2010;41(9):955–9.
doi: 10.1016/j.injury.2009.11.013
Perez RS, Pragt E, Geurts J, Zuurmond WW, Patijn J, van Kleef M. Treatment of patients with complex regional pain syndrome type I with mannitol: a prospective, randomized, placebo-controlled, double-blinded study. J Pain. 2008;9(8):678–86.
doi: 10.1016/j.jpain.2008.02.005
Wang W. Tolerability of hypertonic injectables. Int J Pharm. 2015;490:308–15.
doi: 10.1016/j.ijpharm.2015.05.069
Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA, Chen X, Reichling DB, et al. Hypotonicity induces TRPV4-mediated nociception in rat. Neuron. 2003;39(3):497–511. https://doi.org/10.1016/S0896-6273(03)00462-8 .
doi: 10.1016/S0896-6273(03)00462-8
pubmed: 12895423
Salinas-Abarca AB, Avila-Rojas SH, Barragan-Iglesias P, Pineda-Farias JB, Granados-Soto V. Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain. Euro J Pharm. 2017;797:83–93.
doi: 10.1016/j.ejphar.2017.01.018
Wegner A, Elsenbrunch S, Maluck J, Grigoleit J-S, Engler H, Jager M, et al. Inflammation-induced hyperalgesia: effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia. Brain Behav Immun. 2014;41:46–54.
doi: 10.1016/j.bbi.2014.05.001
Zbacnik TJ, Holcomb RE, Katayama DS, Murphy BM, Payne RW, Coccaro RC, et al. Role of buffers in protein formulations. J Pharm Sci. 2017;106(3):713–33.
doi: 10.1016/j.xphs.2016.11.014
Enright HA, Felix SH, Fischer NO, Mukerjee EV, Soscia D, Mcnerney M, et al. Long-term non-invasive interrogation of human dorsal root ganglion neuronal cultures on an integrated microfluidic multielectrode array platform. Analyst. 2016;141(18):5346–57. https://doi.org/10.1039/c5an01728a .
doi: 10.1039/c5an01728a
pubmed: 27351032