Second phase of formalin‐induced excitation of spinal dorsal horn neurons in spinalized rats is reversed by sciatic nerve block
Bibliographic record
Abstract
Considerable debate persists concerning peripheral vs. central mechanisms underlying the second phase of the nociceptive response in the formalin test in the rat. To gain insight into the neurophysiological basis of this pain, we investigated the effects of block of afferent nerve conduction during the second phase of formalin-evoked excitation of single nociceptive neurons recorded extracellularly from rat spinal dorsal horn segments (L(3-4)) in pentobarbital-anaesthetized, male Sprague-Dawley rats. Rats were spinally transected (T(9)) to examine exclusively peripheral and spinal nociceptive processing. In six control rats, hind paw intraplantar formalin injection (50 microL, 2.5%) induced the typical biphasic increase in the discharge rate of the six wide dynamic range neurons tested. This response consisted of a relatively brief immediate phase (approximately 5 min), followed by decreased firing. An ensuing second phase of elevated discharge began approximately 35 min after injection and persisted to at least 80 min. In this control group, 0.9% saline was applied to the exposed ipsilateral sciatic nerve after onset of the second phase (40 min after formalin injection). In a group of six test rats, application of 2% lidocaine instead of saline reversed the second phase of excitation in all six wide dynamic range neurons examined. When the firing rate was normalized to that at 40 min (100%), the time of saline or lidocaine administration, the rate at 50 min was 120 +/- 7.5% in the saline-treated group and 31 +/- 7.4% in the lidocaine-treated group; following lidocaine treatment firing rate remained markedly less than that before administration throughout the remainder of the recording. It is concluded that: (i) spinal mechanisms alone are not sufficient for induction and maintenance of second phase increased discharge of spinal nociceptive dorsal horn neurons; (ii) descending influences via supraspinal inputs are not causal in the development and maintenance of second phase increased discharge and (iii) tonic input from afferent neurons during the second phase plays a primary and essential role in generating and sustaining the second phase of elevated discharge of dorsal horn neurons and, thus, presumably the second phase of nociceptive scores in the formalin test. The data in this study reveal how much of an altered synaptically elicited response in the spinal dorsal horn can be attributed to postsynaptic plastic changes vs. how much can be simply due to increased synaptic input. The present results are important not only in the context of the formalin test but also in the context of other models related to inflammatory pain and neuropathic pain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".