Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome.

STUDY DESIGN: Although abnormal cutaneous reflex (CR) activity has been identified during gait after incomplete spinal cord injury (SCI), this activity has not been directly compared in subjects with and without the spasticity syndrome. OBJECTIVES: Characterisation of CR activity during controlled rest and 'ramp and hold' phases of controlled plantarflexion in subjects with and without the SCI spasticity syndrome. DESIGN: Transverse descriptive study with non-parametric group analysis. SETTING: SCI rehabilitation hospital. METHODS: Tibialis Anterior (TA) reflexes were evoked by innocuous cutaneous plantar sole stimulation during rest and ramp and hold phases of plantarflexion torque in non-injured subjects (n=10) and after SCI with (n=9) and without (n=10) hypertonia and/or involuntary spasm activity. Integrated TA reflex responses were analysed as total (50-300 ms) or short (50-200 ms) and long-latency (200-300 ms) activity. RESULTS: Total and long-latency TA activity was inhibited in non-injured subjects and the SCI group without the spasticity syndrome during plantarflexion torque but not in the SCI spasticity group. Furthermore, loss of TA reflex inhibition during plantarflexion correlated with time after SCI (ρ=0.79, P=0.009). Moreover, TA reflex activity inversely correlated with maximum plantarflexion torque in the spasticity group (ρ=-0.75, P=0.02), despite similar non-reflex TA electromyographic activity during plantarflexion after SCI in subjects with (0.11, 0.08-0.13 mV) or without the spasticity syndrome (0.09, 0.07-0.12 mV). CONCLUSIONS: This reflex testing procedure supports previously published evidence for abnormal CR activity after SCI and may characterise the progressive disinhibition of TA reflex activity during controlled plantarflexion in subjects diagnosed with the spasticity syndrome.

Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

BACKGROUND: Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. AIM: In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. METHODS: The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. RESULTS: Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. CONCLUSIONS: These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level.

Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.

BACKGROUND: Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses. METHODS: Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 µM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups. RESULTS: Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI. CONCLUSIONS: Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation.