Spinal cord injury in mice amplifies anxiety: A novel light-heat conflict test exposes increased salience of anxiety over heat

Mar 16, 2023Experimental neurology

Spinal cord injury in mice increases anxiety shown by a new test comparing responses to light and heat

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Abstract

At 7 days post-operative, mice with spinal cord injury (SCI) showed increased preference for a heated dark plate compared to uninjured mice.

Both female and male mice with SCI displayed increased preference for the dark plate throughout the TIDAL conflict test.
Female mice remained on the heated-dark plate at higher temperatures than male mice following SCI.
Mice with SCI showed a reduced preference for the dark-heated plate when tested again at 21 days post-operative.
The TIDAL conflict test effectively differentiates between anxiety-like behavior and pain sensitivity in rodents post-SCI.

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Spinal cord injury (SCI) predisposes individuals to anxiety and chronic pain. Anxiety- and pain-like behavior after SCI can be tested in rodents, yet commonly used tests assess one variable and may not replicate effects of SCI or sex differences seen in humans. Thus, novel preclinical tests should be optimized to better evaluate behaviors relating to anxiety and pain. Here, we use our newly developed conflict test - the Thermal Increments Dark-Light (TIDAL) test - to explore how SCI affects anxiety- vs. pain-like behavior, and whether sex affects post-SCI behavior. The TIDAL conflict test consists of two plates connected by a walkway; one plate remains illuminated and at an isothermic temperature, whereas the other plate is dark but is heated incrementally to aversive temperatures. A control mice thermal place preference test was also performed in which both plates are illuminated. Female and male mice received moderate T9 contusion SCI or remained uninjured. At 7 days post-operative (dpo), mice with SCI increased dark plate preference throughout the TIDAL conflict test compared to uninjured mice. SCI increased dark plate preference for both sexes, although female (vs. male) mice remained on the heated-dark plate to higher temperatures. Mice with SCI that repeated TIDAL at 7 and 21 dpo showed reduced preference for the dark-heated plate at 21 dpo. Overall, in female and male mice, SCI enhances the salience of anxiety (vs. heat sensitivity). The TIDAL conflict test meets a need for preclinical anxiety- and pain-related tests that recapitulate the human condition; thus, future rodent behavioral studies should incorporate TIDAL or other conflict tests to help understand and treat neurologic disorders.

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Spinal cord injury in mice amplifies anxiety: A novel light-heat conflict test exposes increased salience of anxiety over heat

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