Related Experiment Video
Updated: Mar 6, 2026
07:12
Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
8.4K
Sigma-1 Receptor and Pain
Manuel Merlos1, Luz Romero1, Daniel Zamanillo1
1Drug Discovery and Preclinical Development, ESTEVE, Barcelona, Spain.
Handbook of Experimental Pharmacology
|March 10, 2017
Summary
Sigma-1 receptor (σ₁R) antagonists show promise for novel pain relief by targeting specific pain pathways. These compounds offer antihypersensitivity effects without altering normal sensory perception, distinguishing them from current analgesics.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Existing analgesics have limitations in efficacy and side effects, creating a need for novel pain-relief mechanisms.
- Preclinical studies indicate the sigma-1 receptor (σ₁R) plays a modulatory role in nociception across various pain types, including neuropathic, inflammatory, and visceral pain.
Purpose of the Study:
- To explore the potential of sigma-1 receptor (σ₁R) antagonists as novel analgesics.
- To investigate the unique antihypersensitivity effects of σ₁R antagonists in pain management.
Main Methods:
- Review of preclinical evidence, including knockout mouse models and studies on σ₁R antagonist efficacy.
- Analysis of findings related to σ₁R expression and function in the central and peripheral nervous systems, particularly dorsal root ganglia (DRG).
- Examination of behavioral, electrophysiological, neurochemical, and molecular data supporting the antinociceptive effects of σ₁R antagonists.
Main Results:
- σ₁R antagonists demonstrate consistent antinociceptive effects in various pain models, notably neuropathic pain.
- σ₁R antagonists modulate receptor and ion channel function, inhibiting neuronal hyperexcitability centrally and peripherally.
- Unlike opioids, σ₁R antagonists do not affect normal sensory thresholds but specifically reverse hypersensitivity in pathological pain conditions.
Conclusions:
- Sigma-1 receptor (σ₁R) antagonists represent a promising therapeutic strategy for chronic pain management.
- Their ability to specifically target pain hypersensitivity without affecting normal sensation offers a distinct advantage over existing analgesics.
Related Concept Videos
01:25Analgesia and Pain Management
2.5K
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
2.5K
01:20Pain
1.7K
Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
1.7K
01:22Opioid Receptors: Overview
5.6K
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
5.6K
01:44Nociception
33.5K
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
33.5K
01:31Sympathetic Signaling
2.7K
Sympathetic signaling, a vital part of the autonomic nervous system, plays a crucial role in mobilizing the body's resources in response to stress or emergencies. It involves the transmission of nerve impulses from sympathetic preganglionic fibers to postganglionic fibers. This results in the release of specific neurotransmitters and activation of adrenergic receptors.
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
2.7K
01:43Thermosensation
34.2K
Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
34.2K