Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

Abstract

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11 weeks, the rats were anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled extracellular recording of T(3) spinal cord neuronal activity. Intrapericardial administration of a mixture of algogenic chemicals (bradykinin, serotonin, prostaglandin E(2) (all at 10(-5)M), and adenosine (10(-3)M)) was applied to activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic receptive properties were examined by applying innocuous (brush and light pressure) and noxious (pinch) cutaneous mechanical stimuli. Diabetes-induced increases in spontaneous activity were observed in subsets of neurons exhibiting long-lasting excitatory responses to administration of the algogenic mixture. Algogenic chemicals altered activity of a larger proportion of neurons from diabetic animals (73/111) than control animals (55/115, P<0.05). Some subtypes of neurons exhibiting long-lasting excitatory responses, elicited prolonged duration and others, had a shortened latency. Some neurons exhibiting short-lasting excitatory responses in diabetic animals elicited a shorter latency and some a decreased excitatory change. The size of the somatic receptive field was increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic mechanical stimulation caused spinal neurons to respond with a mixture of hyper- and hypoexcitability. In conclusion, diabetes induced changes in the spinal processing of cardiac input and these might contribute to cardiovascular autonomic neuropathy in patients with diabetes.

Figure 1

Response pattern of all neurons tested with intrapericardial algogenic chemicals and mechanical stimuli. *P < 0.05. Chi-square test performed on the distribution in the four categories. NR; No response.

Figure 2

Representative traces of response patterns of neurons to intrapericardial algogenic chemicals (IAC). A. Short-lasting excitatory (SL-E) responses in control (left panel) and diabetic (right panel) rats. B. Long-lasting excitatory (LL-E) responses in control (left panel) and diabetic (right panel) rats. C. Inhibitory (I) responses in control (left panel) and diabetic (right panel) rats. For each neuron, the trace of individual action potentials as well as a histogram displaying the activity (impulses/s) is depicted. An expanded view of the trace and histogram showing the initial part of the response is included for all neurons.

Figure 3

Lesion sites and response pattern of T3 spinal neurons excited (●), inhibited (▲), or excited-inhibited/inhibited-excited (¤) by intrapericardial algogenic chemicals (IAC). A. Lesion sites for neurons from control rats and B. from diabetic rats. C. Laminae of the T3 spinal cord segment. D, E. Response patterns for neurons receiving cardiac input located in the superficial (D) and the deeper (E) laminae. The digits above each column represent the number of neurons accounting for that particular column. SL-E; Short-lasting excitatory, LL; Long-lasting, I; Inhibitory. E-I; Excitatory and inhibitory, I-E; Inhibitory and excitatory.

Figure 4

Characteristics of somatic receptive fields of spinal neurons from diabetic and control animals. A. A spinal neuron with low threshold (LT) has a response to brush (Br) and a smaller (or comparative) response to pinch (Pi). B. A wide dynamic range (WDR) neuron responds to brush and to a higher degree to pinch. C. A high-threshold (HT) neurons responds to pinch but not to brush. D, E. Somatic field properties for diabetic and control neurons responding to somatic (D) and cardiosomatic stimuli (E). The digits above each column represent the number of neurons accounting for that particular column.

Figure 5

Somatic field sizes of spinal neurons from diabetic and control animals. A. Areas of somatic receptive fields for small- (S), medium- (M) and large-sized (L) cells. B. Distribution of somatic field sizes for all neurons receiving somatic input, i.e. somatic and cardiosomatic neurons. * P < 0.05 compared to control neurons. C, D. Distribution of somatic field sizes for somatic (C) and cardiosomatic (D) neurons. * P < 0.05 compared to control neurons. The digits above each column represent the number of neurons accounting for that particular column.