Acute & Tonic Pain
Pain is a necessary protective reaction that alerts the body to the presence of actual or potential tissue damage such as a sprained ankle, burn or a paper cut. Under normal conditions, stimuli approaching or exceeding harmful intensity are transmitted from different locations in the body to the brain that, in turn, interprets this information as a sharp and severe sensation of pain.
Transpharmation offers standard pain tests utilizing mechanical, chemical and thermal stimuli. These assays are widely and reliably used to reveal the efficacy of new analgesics.
Models
The formalin test is a well-established tonic pain assay based on a chemical stimulus. Unilateral subcutaneous injection of formalin into the hindpaw produces a biphasic nocifensive response: an early phase (0-10 min), driven by direct activation of primary afferent sensory neurons, followed by a late phase (15-60 min) reflecting the combined effects of ongoing afferent input, spinal central sensitization, and local inflammatory processes. This temporal dissociation gives the model strong mechanistic resolution: centrally acting analgesics (e.g., opioids) and NSAIDs preferentially suppress the late phase, while agents acting on acute nociceptive transduction act on the early phase, allowing early characterization of a candidate’s site and mode of action.
Capsaicin, the pungent ingredient in hot peppers, activates TRPV1-positive nociceptors and triggers substance P release, producing burning pain together with primary hyperalgesia (thermal and mechanical, at the injection site) and secondary mechanical hyperalgesia/allodynia in the surrounding, non-injured skin, a central sensitization phenomenon that closely mirrors the sensory profile seen in neuropathic pain patients. At Transpharmation, capsaicin is administered by intraplantar injection (3 μg/10 μL) in mice and rats; mechanical allodynia is assessed from 30 min post-injection, alongside complementary readouts such as von Frey to characterize a compound’s analgesic potency.
The tail flick test is one of the oldest and most widely used acute pain assays, based on a thermal stimulus. Radiant heat is applied to the tail; the animal’s withdrawal (tail flick) automatically terminates the stimulation, and the nociceptive reaction latency is recorded. The response is mediated primarily by a spinal reflex circuit, with supraspinal modulation, making the assay a simple, robust readout of acute nociceptive sensitivity. It is particularly sensitive to analgesic compounds, which reliably and dose-dependently increase tail flick latency, allowing early characterization of a candidate’s analgesic potency.
The hot plate test is an acute pain test based on the use of a thermal stimulus. The plate, heated at a constant temperature (52 °C or 56 °C), produces two behavioral components that can be measured in terms of their reaction times (with a cut-off time set at 30 seconds to prevent tissue damage), namely paw licking and jumping. Both are stereotyped behaviors in rodents (rats and mice) and are considered to be supraspinally integrated responses. This assay is widely and reliably used for revealing the potency of new analgesics.
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Humanized Models PXB humanized-liver mice
SPIDAR Rapid analgesic screening
Transgenics Genetically modified mice
Have a program in mind?
Talk to a Transpharmation researcher about your study design and timelines.