Dysesthesias and self-mutilation in humans and subhumans: A review of clinical and experimental studies

Levitt, M.

doi:10.1016/0165-0173(85)90027-x

Cited by 95 publications

(21 citation statements)

References 216 publications

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“…Another source of evidence for induction of dysesthesias by spinal lesions has come from reports of self-mutilation (autotomy) of the distal portion of a limb by some monkeys following anterolateral chordotomy (Levitt and Levitt, 198 1;Levitt, 1985). The autotomy occurs contralateral to the lesion, and dysesthesias often occur in humans on the side opposite an anterolateral chordotomy (e.g., White, 1963;Pagni, 1976).…”

Section: Discussionmentioning

confidence: 99%

Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy

1990

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Macaca nemestrina monkeys received unilateral interruption of the spinothalamic tract, producing contralateral hypalgesia and a bilateral decrease in amplitude of the flexion reflex. These effects on operant escape and reflex responses to electrocutaneous stimulation (ES) were monitored for months to evaluate relationships between the extent of each lesion and the presence or absence of recovery from the early postoperative deficits. Before surgery, the animals were trained to perform an operant response that terminated ES to the lateral calf of either leg. The durations of ES tolerated by each monkey were inversely related to stimulus intensities within the pain sensitivity range of human subjects. The vigor of operant escape responses and the frequency of intertrial pulls of the manipulandum were directly related to stimulus intensity. Following anterolateral chordotomy at an upper thoracic level, these measures revealed a contralateral hypalgesia for each animal. Operant responsivity to stimulation contralateral to the lesion recovered to control levels for 7 animals (group R). Sustained contralateral recovery of operant reactivity was not observed for 8 monkeys (group U). Most of the lesions in groups R and U were similar in extent and location, involving the classical distribution of the spinothalamic tract (in the anterolateral and ventral columns). Thus, recovery was not determined solely by lesion configuration. However, when recovery did occur, it was associated with medially extensive lesions. A subgroup of 3 unrecovered animals received superficial lesions that did not substantially involve the gray matter or the ventral columns. For all animals, reflex magnitudes were initially diminished bilaterally and then increased over months of testing. Reflex recovery was greater for the animals that demonstrated recovery of intentional reactions to nociception (group R). An ipsilateral hyperreflexia became apparent for group R. Contralateral recovery to normal levels was observed for group R but not for group U. The time course of recovery for operant and reflex responses clearly differed, indicating that different processes determined changes in these spinal and supraspinal reactions to nociceptive stimulation.

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Section: Discussionmentioning

confidence: 99%

Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy

1990

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“…To date, there is no evidence that sensory dysesthesia results from RTX chemoaxotomy. This is potentially a consequence of the anatomical distinctions between this approach and surgical dorsal rhizotomy, which can produce these undesirable effects in humans and in animal models (70,71). The crucial differences between cell deletion and cell axotomy underscore the value of continued investigation into highly specific molecular approaches for pain control.…”

Section: Peripheral and Central Delivery Of Rtx In Ratsmentioning

confidence: 99%

Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons

Sapio

Neubert

LaPaglia

et al. 2018

Journal of Clinical Investigation

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Authorship note: MRS and JKN contributed equally to this work. Conflict of interest:MJI is an inventor on US patent US 8338457 B2, "Selective ablation of pain-sensing neurons by administration of a vanilloid receptor agonist, " issued to the NIH, and is on the scientific advisory board of Ark Animal Health. JDH has received research support through a cooperative research and development agreement with Sorrento Therapeutics. JKN, ELR, and RMC are employees of Velocity Laboratories, a company that provides fee-for-service behavioral testing using operant pain assays.

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“…Note that these clinical signs occur on the side of the animal that does not display motor deficits. Levitt [64] concluded that the "deafferentation syndrome" was released by interrupting spinothalamic tracts, and that the incidence was genetically variable (incidence of 31% in a multispecies group to 95% in a group of 19 stump-tailed macaques), and that some of the variability might be related to variability in the location of the spinothalamic tracts (sometimes in the posterolateral funiculus and sometimes in the ipsilateral anterolateral funiculus) [61,64]. In those earlier studies, monkeys that had sensorimotor deficits did not display disruptions of activity level, feeding, grooming (normal dermatomes), libido, vocalization, or social behavior.…”

Section: Contributions and Implications: Safety Assessmentmentioning

confidence: 99%

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

et al. 2012

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Dysesthesias and self-mutilation in humans and subhumans: A review of clinical and experimental studies

Cited by 95 publications

References 216 publications

Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy

Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy

Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

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