Nociceptive behavioral responses to chemical, thermal and mechanical stimulation after unilateral, intrastriatal administration of 6-hydroxydopamine

Abstract

The basal ganglia are involved not only with motor processes such as posture, pre-movement planning and movement initiation, but also with the processing and modulation of nociceptive somatosensory information. In the current studies, unilateral, intrastriatal 6-hydroxydopamine (6-OHDA) was used to investigate how dopamine depletion alters nociceptive behavioral responses to chemical, thermal and mechanical stimulation in rats. Compared to control rats injected with intrastriatal saline, rats depleted of dopamine displayed increased nociceptive responses to chemical stimulation of the face and hyperalgesic responses to thermal stimulation of the hind paw without alterations in rearing behavior or body weight gain. Minor changes were observed in the response to mechanical stimulation of the hind paws and face. These data provide further evidence that the dopaminergic nigrostriatal pathway plays a role in the modulation of nociceptive information.

Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion

“…Since the direct dopaminergic projection from VTA exerts an inhibitory effect on electrical responses in the prefrontal cortex to mechanical noxious stimulation (Sogabe et al, 2013), the ascending dopaminergic projections should be considered to forward the future experiments. Previous studies have shown the effects of dopamine depletion during adulthood on nociceptive responses (Saade´et al, 1997;Takeda et al, 2005;Tassorelli et al, 2007;Chudler and Lu, 2008); however, these results were not always consistent with those of the present study. Decreased latency of withdrawal responses to mechanical and/or thermal stimuli has been observed in the hemi-Parkinson rat model (Takeda et al, 2005;Chudler and Lu, 2008), as also has the hyperalgesic response to a formalin injection (Tassorelli et al, 2007;Chudler and Lu, 2008).…”

“…Previous studies have shown the effects of dopamine depletion during adulthood on nociceptive responses (Saade´et al, 1997;Takeda et al, 2005;Tassorelli et al, 2007;Chudler and Lu, 2008); however, these results were not always consistent with those of the present study. Decreased latency of withdrawal responses to mechanical and/or thermal stimuli has been observed in the hemi-Parkinson rat model (Takeda et al, 2005;Chudler and Lu, 2008), as also has the hyperalgesic response to a formalin injection (Tassorelli et al, 2007;Chudler and Lu, 2008). The discrepancy between the results of the present and previous studies is attributable to the anatomical extent (unilateral or bilateral lesion in the dopaminergic neural system) and developmental period (adulthood or neonatal) of dopamine depletion.…”

“…These clinical reports are also supported by experimental data, as detailed below. Rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions in the nigrostriatal dopaminergic neurons show hypersensitivity to mechanical (Saadeé t al., 1997;Takeda et al, 2005) and thermal (Saadeé t al., 1997;Chudler and Lu, 2008) stimuli. Furthermore, unilateral 6-OHDA-treated rats exhibited hyperalgesic response to pain-inducing chemical stimuli (Tassorelli et al, 2007;Chudler and Lu, 2008).…”

Animal models of the non-motor features of Parkinson's disease

“…In one experiment rats were injected unilaterally with 5 μg of 6-OHDA into the STR and examined for changes in nociceptive behavior. Results revealed a hyperalgesic response to chemical stimulation of the face, and mechanical and thermal stimulation of the hind paws over the course of three weeks, with a severe loss of TH-ir neurons in the SNpc in the lesioned rats (Chudler and Lu, 2008). A unique method was used to by Gravotta et al (2011) to analyze circadian rhythm alterations in the 6-OHDA exposed rat.…”

Mesocortical dopamine system modulates mechanical nociceptive responses recorded in the rat prefrontal cortex

“…In animal studies, microinjections of DA into the ACC reduced autotomy scores in a sciatic neurotomy model [15]. Behavioral in vivo studies of pain have demonstrated that DA depletion induces significant changes in thresholds for noxious stimuli [16,17]. Six-hydroxydopamine (6-OHDA) lesions in the VTA induced hyperalgesia in acute and chronic pain models [18].…”