Nociceptive Pain Drug Discovery Service

Pain is a complex subjective phenomenon that involves the participation of many receptors in different tissues and organs. It is usually divided into acute and chronic based on response time, whereas nociceptive pain mostly is acute. It is generally believed that pain signals originate from the sensitization of peripheral nociceptors and dorsal horn neurons, but nociceptive pain is often mixed with various underlying factors, so little is known about basic pain processing linked to nociception. As a leading company in biotechnology, Creative Biolabs provides an efficient and stable one-stop nociceptive pain drug discovery service through our stable and reproducible experimental data.

Background and Mechanism of Nociceptive Pain

The source of nociceptive pain is varied, but most of them are neuropathic. Peripheral somatosensory neurons are the longest cells in our body and have a complex pseudo-unipolar morphology. When the peripheral axon is traumatized and severed, the nerve stump develops swelling and terminal balls, which then grow into elongated protrusions. Only when these nerve endings are close enough together is it possible to reconnect and grow. If nerve regeneration is blocked, the terminal bulb and surrounding glial and excess cellular components can become large neuromas. Both the neuroma and the damaged nerve itself produce spurious ectopic discharges and cause a pain response. The persistent state of pathological hyperexcitability of nociceptive afferents is thought to be required for the development of most neuropathic pain.

Fig 1. Nociception and inflammatory responses resulting from tissue damage. (Araujo, 2020)

The specific molecular mechanisms that generate nociceptive pain are still not fully understood, but studies suggest that neuropathic degeneration of damaged nerves and corresponding damage to sensory ganglia and large-scale remodeling of nerve fibers may be involved. A striking feature of this remodeling is the dramatic downregulation of K⁺ channel genes, and loss of this channel is expected to lead to depolarization and increased excitability of nerve cells. At the same time, nociceptors also have their intrinsic activation thresholds, and the phospholipase C (PLC) /Ca signaling pathway can contribute to inflammatory hypersensitivity and excitability.

Experimental Models of Nociceptive Pain

As pain is subjective, measurement of pain is often also subjective judgment through animal models and emotional, physiological, cognitive, and behavioral aspects, as well as monitoring of mechanical thresholds and after-sensory duration, or cerebral cortex and neural excitability analysis through neuroimaging. Here at Creative Biolabs, we provide you with stable neuropathic pain models with mice and assess pain and tolerance thresholds, record and analyze sensory data through ECG and EMG.

Fig 2. Simplified schematic of a nociceptive neuron. (Du, 2018)

Inhibition of Nociceptive Pain

Currently, there is no final clinical solution for nociceptive pain, and medication can only be determined based on manifestations and symptoms. Opioids have long been used for pain relief, but these drugs are prone to cognitive and behavioral side effects and problems with tolerance and addiction. Creative Biolabs assist our clients with their strategies for peripheral analgesia including topical application of nonspecific drugs like nonspecific voltage-gated Na⁺ channel blockers, such as lidocaine, or drugs specific for broadly expressed targets, like Ziconotide, a Conotoxin inhibitor of N-type voltage-gated Ca²⁺ channels. These strategies can be effective but often result in a complete loss of sensory and motor fiber activity. Besides, we also monitor the content of pain-related molecules and provide you with comprehensive and reliable analysis data through molecular biology methods such as immunofluorescence staining.

Fig 3. Physiological data were recorded during pain tolerance experiments. (Thiam, 2019)

Services at Creative Biolabs

Research on nociceptive pain is always accompanied by many potential confounding factors. Years of experience have made Creative Biolabs deeply understand the importance of longitudinal research on these discrete mechanisms. Therefore, with our excellent experts and cutting-edge technology, we provide our clients with one-stop nociceptive pain solutions. In addition to screening, synthesizing, and analyzing your drug molecules of interest, we provide stable animal or in vitro models to measure and evaluate pain sensation, or perform imaging analysis on neuronal cells, protein/gene expression, and drug-targeting assays at the molecular level. No matter what stage your research is in, we can propose a feasible and reliable solution for you. So please do not hesitate to contact us and discuss your needs.

References

1. Araujo, D.S.M.; et al. TRPA1 as a therapeutic target for nociceptive pain. Expert Opinion on Therapeutic Targets. 2020, 10: 997-1008.
2. Du, X.; et al. M-type K+ channels in peripheral nociceptive pathways. British Journal of Pharmacology. 2018, 175: 2158-2172.
3. Thiam, P.; et al. Exploring deep physiological models for nociceptive pain recognition. Sensors. 2019, 19: 4503.