Eric H. Chudler

The role of the basal ganglia in nociception and pain

&NA; The involvement of the basal ganglia in motor functions has been well studied. Recent neurophysiological, clinical and behavioral experiments indicate that the basal ganglia also process non‐noxious and noxious somatosensory information. However, the functional significance of somatosensory information processing within the basal ganglia is not well understood. This review explores the role of the striatum, globus pallidus and substantia nigra in nociceptive sensorimotor integration and suggests several roles of these basal ganglia structures in nociception and pain. Electrophysiological experiments have detailed the non‐nociceptive and nociceptive response properties of basal ganglia neurons. Most studies agree that some neurons within the basal ganglia encode stimulus intensity. However, these neurons do not appear to encode stimulus location since the receptive fields of these cells are large. Many basal ganglia neurons responsive to somatosensory stimulation are activated exclusively or differentially by noxious stimulation. Indirect techniques used to measure neuronal activity (i.e., positron emission tomography and 2‐deoxyglucose methods) also indicate that the basal ganglia are activated differentially bo noxious stimulation. Neuroanatomical experiments suggest several pathways by which nociceptive information may reach the basal ganglia. Neuroanatomical studies have also indicated that the basal ganglia are rich in many different neuroactive chemicals that may be involved in the modulation of nociceptive information. Microinjection of opiates, dopamine and gamma‐aminobutyric acid (GABA) into the basal ganglia have varied effects on pain behavior. Administration of these neurochemicals into the basal ganglia affects supraspinal pain behaviors more consistently than spinal reflexive behaviors. The reduction of pain behavior following electrical stimulation of the substantia nigra and caudate nucleus provides additional evidence for a role of the basal ganglia in pain modulation. Some patients with basal ganglia disease (e.g., Parkinsons disease, Huntingtons disease) have alterations in pain sensation in addition to motor abnormalities. Frequently, these patients have intermittent pain that is difficult to localize. Collectively, these data suggest that the basal ganglia may be involved in the (1) sensory‐discriminative dimension of pain, (2) affective dimension of pain, (3) cognitive dimension of pain, (4) modulation of nociceptive information and (5) sensory gating of nociceptive information to higher motor areas. Further experiments that correlate neuronal discharge activity with stimulus intensity and escape behavior in operantly conditioned animals are necessary to fully understand how the basal ganglia are involved in nociceptive sensorimotor integration.

SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation

The activity of primary somatosensory (SI) cortical nociceptive neurons was recorded while the monkeys performed a psychophysical task in which they detected small increases in skin temperature superimposed on noxious levels of thermal stimulation. The detection latency to these stimuli, expressed as detection speed, was used as a measure of the perceived intensity of sensation. Two-thirds of the neurons that responded to noxious thermal stimulation increased their discharge in response to graded increases in stimulus intensity. The remaining neurons responded to noxious thermal stimulation, but did not grade their response with the intensity of the stimulus. The response of SI nociceptive neurons that encode the intensity of noxious thermal stimulation was significantly correlated with the monkeys detection speed. We conclude that SI nociceptive neurons are involved in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.

A key role of the basal ganglia in pain and analgesia - insights gained through human functional imaging

The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain.

Physiological properties of intradental mechanoreceptors

A major role of tooth receptors in signaling overt or impending tissue damage (nociception) has been previously established by substantial evidence from mechanical, thermal and chemical stimulation of exposed dentin. We report evidence showing that some intradental receptors in canine teeth of the cat detect mechanical transients applied to intact enamel. This new finding suggests that dental innervation may play an important non-nociceptive role in oral function such as detecting tooth contact during mastication and swallowing.

The assessment of pain by cerebral evoked potentials

Cerebral evoked potentials have been recorded by various means for nearly 100 years [ 14

Multisensory convergence and integration in the neostriatum and globus pallidus of the rat

The extracellular response properties of neurons in the caudate-putamen (CPu), globus pallidus (GP) and lateral amygdaloid nucleus (La) evoked by auditory and somatosensory stimuli were investigated. A total of 61 neurons in these areas responded either singly to somatosensory stimulation (unisensory), or to both somatosensory and auditory stimulation (multisensory). Higher rates of somatosensory stimulation reduced the response magnitude of CPu neurons more than that of GP neurons. In multisensory neurons, combined somatosensory and auditory stimulation compared to unisensory stimulation resulted in three characteristic response patterns: enhancement, depression or interaction. Temporal misalignment of the peak frequency latencies evoked by auditory and somatosensory stimulation altered the response magnitude in the majority of neurons. The response properties and anatomical connectivity of CPu and GP neurons suggest that the observed multisensory integrative effects may be used to facilitate motor responses to low intensity stimuli.

Response properties of neurons in the caudate-putamen and globus pallidus to noxious and non-noxious thermal stimulation in anesthetized rats

To investigate the possible mechanisms by which neurons in the caudate-putamen (CPu) and globus pallidus (GP) participate in pain and nociception, the present study characterized the response properties of CPu and GP neurons to non-noxious and noxious thermal stimuli in anesthetized rats. Nociceptive CPu and GP neurons were capable of encoding noxious thermal stimuli and 79% of these thermally responsive neurons also responded to noxious mechanical stimuli. Thermally responsive neurons were activated during the phasic rise and fall of the thermal shift in addition to the plateau temperature. The ability of CPu and GP neurons to encode noxious thermal stimulation intensity and respond during the dynamic phase of the stimulus suggests that these neurons may contribute to the behavioral response to minimize bodily harm.

Trigeminal ganglion neuronal activity and glial fibrillary acidic protein immunoreactivity after inferior alveolar nerve crush in the adult rat

&NA; Nerve injury to the mandibular division of the trigeminal nerve has been shown to cause satellite cell reactions that extend beyond the mandibular division of the trigeminal ganglion into the maxillary and ophthalmic divisions. The goal of this study was to determine whether any physiological abnormalities correlated with this dispersal of satellite cell reaction. We investigated the electrophysiological and satellite cell glial fibrillary acidic protein immunoreactivity (GFAP‐IR) changes that occur within the trigeminal ganglion 3, 10 and 59 days after a crush injury of the inferior alveolar nerve (IAN). At 3 days after IAN crush, there were no mechanically‐evoked responses to ipsilateral stimulation of the skin and intraoral structures (e.g., mandibular incisor, lower lip and rostral mandibular gingiva) innervated by the IAN. However, the peripheral representations of the auriculotemporal, mylohyoid, lingual and maxillary nerve were intact and no abnormal responses to mechanical stimulation were detected to stimulation of tissue innervated by these nerves. By 10 days after the IAN crush, mandibular neurons responded to mechanical and electrical stimuli of the peripheral receptive field of the IAN, but with slower conduction velocities and higher electrical thresholds compared to control values. These abnormal electrophysiological response characteristics persisted 59 days following nerve injury. At 3, 10 and 59 days after IAN crush, 3–4% of the recorded mandibular neurons displayed spontaneous activity that was never observed in rats without nerve injury. Spontaneous activity was also never observed in neurons recorded in the maxillary or ophthalmic divisions of the trigeminal ganglion. Intense GFAP‐IR in satellite cells was observed surrounding a mean of 131.7 neurons/section within the mandibular division of the trigeminal ganglion 3 days after nerve injury and around 50.3 neurons/section at 10 days. GFAP‐IR was also present surrounding 16.5 and 10.3 neurons/section in the maxillary division of the trigeminal nerve at 3 and 10 days, respectively. At 59 days after IAN crush, GFAP‐IR satellite cells were found around 22.9 neurons/section in the mandibular division of the trigeminal nerve, but were not found elsewhere in the trigeminal ganglion. The more extensive distribution of neurons encircled by satellite cell GFAP‐IR compared to the trigeminal ganglion region containing abnormal electrophysiological responses demonstrates that abnormal neuronal signaling may not be characteristic of trigeminal ganglion neurons that are surrounded by GFAP injury reactions. However, the persistence of GFAP‐IR 59 days after nerve injury suggests that satellite cell GFAP is involved in the long‐term recovery of injured neurons.

Tooth pulp-evoked potentials in the monkey: Cortical surface and intracortical distribution

&NA; The distribution of tooth pulp‐evoked potentials (TPEPs) was characterized in the primary motor (MI), primary somatosensory (SI) and secondary somatosensory (SII) cortices of the monkey. Bipolar electrical tooth pulp stimulation elicited TPEP components P23 and N44 over SI, P26 and N72 over MI and P72, N161, P280, N420, P561 and N662 over SII. Muscular artifacts and extradental input did not affect the TPEP as demonstrated by experiments using a neuromuscular blocking agent and removal of the pulp, respectively. The short latency TPEPs recorded over SI and MI were evoked by low stimulus intensities and activation of A&bgr; nerve fibers, whereas the long latency TPEPs recorded over SII required higher stimulus intensities and the additional recruitment of A&dgr; nerve fibers. Intracortical recordings revealed polarity reversals of components P23 and N44 in area 3b, P26 and N72 in area 4 and P72, N161, P280, N420, P561 and N662 in the upper bank of the lateral sulcus (SII). Evidence presented in this study suggests that TPEPs recorded from SI and MI relate to non‐nociceptive mechanisms while TPEPs recorded from SII relate to nociceptive mechanisms.

A role for neuroscientists in engaging young minds.

Neuroscience receives little attention in elementary school education, although students at this age are active explorers of their environment and can relate easily to exercises that involve the science of their senses. The neuroscientist has an important role in supporting elementary educators who might be uncomfortable with teaching science. To encourage such scientist–teacher interactions, changes must be made in the culture of the scientific community to promote these partnerships, with the ultimate goal of improving neuroscience literacy.