Altered hippocampal long-term potentiation after peripheral nerve injury in mice.

It has been clinically reported that patients with chronic pain often have accompanying cognitive deficiency, which hampers efficient medical treatment. In the present study, we investigated whether hippocampal synaptic plasticity, which has been considered to be a cellular model of learning and memory, could be influenced by chronic pain conditions using a murine model of neuropathic pain prepared by partial ligation of the sciatic nerve (the Seltzer model). In slices obtained from neuropathic animals, tetanus-induced long-term potentiation of CA1 hippocampal synaptic transmission was impaired, whereas long-term depression induced by low-frequency stimulation was similar in neuropathic and sham-treated (control) animals. Bath application of the beta-adrenoceptor agonist isoproterenol or the beta-adrenoceptor antagonist propranolol diminished the difference of synaptic plasticity between neuropathic and control mice. In the presence of isoproterenol, long-term potentiation was successfully induced in neuropathic mice. By contrast, long-term potentiation in sham-treated mice was impaired by propranolol which did not alter the already impaired long-term potentiation after peripheral nerve injury. These results suggest that beta-adrenergic functions are changed in chronic pain conditions, which may underlie the deficiency of long-term potentiation.