Spasticity is one of a multitude of factors that cause hypertonia. Spasticity is clinically defined as a phenomenon of velocity-dependent increase in resistance to external stretch, i.e., exaggerated stretch reflex (1). Alteration in spasticity can be a sign or reflection of underlying pathology, e.g., increased spasticity can be caused by urinary tract infection. Severity of spasticity could also be affected by many other factors, such as posturing, anxiety, and weather (2). Neurologically stable spinal cord-injured patients may present, or may be perceived to have, different levels of spasticity in the winter time (3) or even with strong air conditioning (4). However, these results are mixed (2). There are also case reports which showed that spasticity was increased by cold weather in stroke patients (5, 6). This pattern of change usually requires adjustment in treatment plan or options, such as increasing dose of botulinum toxin in the winter time.

Cold exposure increases the severity of spasticity in the affected muscles and overall muscle tone of the whole body. This clinical observation of increased tone in response to acute cold challenge is part of common thermal defense responses, including cutaneous vasoconstriction and shivering and non-shivering thermogenesis. The overall increase in muscle tone before the onset of overt shivering is termed “thermal muscle tone” (7). It is related to activation of the fusimotor drive via the thermoregulatory reflex during cold exposure (8). In an animal study (8), the efferent fusimotor activity to the rat gastrocnemius muscle was found to increase when the trunk skin was cooled for as short as 30 s by a water-perfused jacket and returned to normal when the skin was rewarmed. The cold-induced fusimotor activation enhanced the afferent discharges of the stretched muscle. However, this activation was blocked by inhibition of neurons in the rostral medullary raphe. In other words, thermal muscle tone is centrally mediated.

Spastic hypertonia consists of reflex-related component, i.e., hyperreflexia and non-reflex-related component (9–12). The hyperreflexia-related spaticity accounts for the commonly observed phenomenon of velocity-dependent increase in resistance. It is indicative of hyperexcitability of spinal stretch reflex circuits as a result of imbalanced descending pathways secondary to disinhibition after stroke (12). On the other hand, a number of peripheral muscular changes can contribute to hypertonia (13, 14). These factors include muscle fiber changes and altered tendon compliance. These peripheral changes may be secondary to paresis. When a paralyzed muscle is maintained in a shortened joint position, for example, a flexed elbow joint position, the muscle is often able to adapt to this situation and becomes shortened. As a result, sarcomeres are lost, muscle fibers become stiffer, and mechanical resistance to stretch increases, i.e., hypertonia (15). Additionally, there is an accumulation of viscous intramuscular substances, such as hyaluronan (16). These changes in the mechanical properties of muscles may gradually lead to increased muscle stiffness (17). These components are not adequately differentiated in common clinical examinations (18) or even in quantitative assessments of muscle stiffness in the laboratory setting (19).

Cold-induced changes in the severity of spasticity are easily perceived by patients and are often assessed with clinical scales, such as modified Ashworth scale (MAS). However, it remains unknown which components of spasticity are influenced by cold exposure. Since cold-induced thermal muscle tone is centrally mediated, its effect on spastic muscles could be quantified by changes in spasticity in the affected muscle in responses to experimentally imposed cold challenge to the contralateral limb. In this way, the peripheral mechanisms in the spastic muscle are not altered by cold stimulation. To achieve this goal, we have developed a thermal-stimulation/biomechanical-quantification approach in this study. In particular, we used a thermal stimulator to provide a brief yet controlled heat/cold stimulation to the contralateral hand in stroke survivors, while an established biomechanical approach was used to quantify the response from the spastic–paretic elbow flexors (20–23). Resistance to slow stretching (e.g., 5°/s) is considered to reflect the passive and non-reflex property of spastic muscles. The difference in resistance between fast (e.g., 100°/s) and slow stretching thus represents the reflex component of spastic muscles. As such, this unique approach allowed us to examine the effects of cold exposure on different components of spasticity.

Thirteen spastic–paretic hemiplegic stroke subjects (five females, eight males, aged 53–78 years, history of stroke: 68 ± 42 months) participated in the experiment. Subjects were recruited from the TIRR Memorial Hermann outpatient clinic. Inclusion criteria were those who: (1) had spastic hemiplegia secondary to a single ischemic or hemorrhage stroke; (2) had a history of at least 6 months poststroke; (3) had elbow flexor spasticity of the impaired side greater than 0, but less than 3 (rated by MAS) in order to have sufficient range of motion for stretching; (4) were able to understand and follow instructions related to the experiment; and (5) were able to give informed written consent. The exclusion criteria were those who: (1) had a history of multiple strokes or bilateral involvement and (2) had presence of contracture that would limit full elbow range of motion on the impaired side. Spasticity of elbow flexors was MAS of 1+ and 1 in this experiment. The experiment was approved by the UTHealth Committee for the Protection of Human Subjects. All subjects gave written informed consent prior to participation.

For this study, we adopted our recent experimental setup (23, 24). The subjects were seated on a height adjustable chair. The spastic limb was safely secured in a customized apparatus with the shoulder at approximately 45° of abduction and 30° of flexion. The center of the elbow joint and the axis of rotation of the servo motor were perfectly aligned to prevent translation and rotation of the arm. Four vertical plates were used to secure the forearm at the proximal and distal forearm (Figure 1). The subjects were instructed to keep the wrist, hand, and fingers relaxed during external stretching. The other arm of the subject rested symmetrically on another table.

Total torque was significantly affected by both stretching speed and thermal stimulation (Figure 2). According to the two-way ANOVA analyses, there were main effects of SPEED [F(1,12) = 27.65, p < 0.0001] and THERMAL [F(2,24) = 3.88, p = 0.035]. No significant interactions were observed. Averaged across different thermal conditions, total torque was significantly greater at 100°/s (5.98 Nm) than at 5°/s (2.82 Nm). Averaged across different speeds, total torque was 4.33 Nm at BASELINE, 4.84 Nm during COLD, and 4.02 Nm during HEAT (Figure 3A).

When normalized to the total torque at BASELINE, the percent change in total torque was also speed and temperature-dependent (Figure 4). Two-way ANOVA analyses showed main effects of SPEED [F(1,12) = 0.473 p = 0.505], TEMP [F(1,12) = 9.078 p = 0.011] and a significant interaction SPEED × TEMP [F(1, 12) = 6.907, p = 0.022]. Tukey post hoc tests further revealed that the percent torque change was significantly greater by COLD (18.1%) than HEAT (−8.7%) at slow speed, but there was no difference in torque change between COLD (4.0%) and HEAT (−3.9%) at fast speed of stretching. Overall, COLD increased total torque by 11.0%, while HEAT decreased total torque by 6.3%.

The reflex torque, obtained visually by subtracting the gray bars from the corresponding black bars on Figure 3A, however, did not differ significantly across three thermal conditions [F(1,12) = 0.661, p = 0.551]. They were 3.29, 3.01, and 3.15 Nm for BASELINE, COLD, and HEAT, respectively (Figure 3B).

In this experiment, a novel thermal-stimulation/biomechanical-quantification approach was used to quantify spastic hypertonia of elbow flexors in stroke subjects when thermal stimulation was applied to the contralateral hand in three thermal conditions: BASELINE, COLD, and HEAT. There were no changes in the biomechanical configuration or sensorimotor condition of the spastic limb during subsequent external stretches across different thermal conditions. The thermal-stimulation/biomechanical-quantification approach allows a unique opportunity to individually assess the reflex and non-reflex components of spastic hypertonia. In addition to confirming velocity-dependent increases in total torque, the novel findings included (1) total torque was significantly increased after COLD, but not HEAT as compared to BASELINE and (2) reflex torque did not differ significantly across the three thermal conditions. Our findings of no significant change in reflex torque across thermal conditions and increased total torque after cold stimulation suggest that cold stimulation specifically modulates the non-reflex component without affecting the reflex component in stroke survivors.

This study found that cold stimulation primarily alters non-reflex, passive stiffness of spastic muscles in stroke subjects. It is important to point out that many factors could contribute to non-reflex, passive stiffness, such as viscoelasticity of the muscle (14, 25), changes in muscle property (26), and accumulation of extracellular deposits (27). Unfortunately, we are not able to differentiate these factors in this study. Our finding was consistent with reports from an earlier study (7). A brief cold exposure specifically increased overall muscle tone, but did not alter fine neuromotor control during force production. The increase in the non-reflex response and the overall muscle tone during cold exposure suggests a central mechanism. This cold-induced increase in overall muscle tone is likely part of cold-defense mechanisms via activation of neurons in the rostral medullary raphe (8). In contrast, no effect of cold stimulation on the reflex component suggests that the excitability of reflex pathways is not affected.

The finding of no significant effect of cold stimulation on the reflex component is not trivial. The stretch reflex is a monosynaptic reflex that provides automatic regulation of skeletal muscle. Skeletal muscle contains extrafusal and intrafusal muscle fibers. Extrafusal fibers are innervated by alpha motor neurons, mediating muscle contraction. Intrafusal fibers constitute the muscle spindle. These intrafusal fibers are innervated by gamma motor neurons. The muscle spindle serves as mechanoreceptors for the muscle and provides feedback to the central nervous system. When a muscle is lengthened by passive stretch, both the change in muscle length and its rate are detected by muscle spindles (primarily group Ia and II afferent fibers). Golgi tendon organs also send information on muscle tension through group Ib afferent fibers. The increase in neuronal activity in these fibers in turn increases alpha motor neuron activity in the stretched muscles through the stretch reflex. This causes the extrafusal muscle fibers to contract and thus resist the muscle lengthening or stretching. Meanwhile, Ia afferent fibers also synapse with Ia inhibitory interneurons, producing relaxation of the antagonist muscles (“reciprocal inhibition”). In summary, gamma motor neurons regulate muscle spindles (fusimotor system) and thus the reflex sensitivity.

By subtracting the torque response at 5°/s from that at 100°/s, reflex torque reflects the aggravated reflex response to a fast external stretch. This velocity-dependent reflex torque is likely mediated by velocity-sensitive spindle afferent inputs (Ia and II spindle afferents) (22, 28) and hyperexcitable spinal motor neurons (9, 12, 29). It is viewed as a result of unopposed descending inputs to spinal motor neuron pools from hyperexcitable medial reticulospinal pathways (12, 30). Cold stimulation is known to relate to the activation of the fusimotor drive via the thermoregulatory reflex (8). The cold-induced fusimotor activation enhanced the afferent fusimotor discharges. No cold effect on the reflex torque suggests that the cold-induced fusimotor activation does not increase stretch reflex responses in spastic flexors. These findings are in general in consistence with previous findings (31, 32). These studies reported that the reflex amplitude was not disproportionally affected by changes in fusimotor function—by an after-effect of voluntary contraction, cutaneous mechanical stimulation, or electrical nerve stimulation. However, our findings extended previous reports that the fusimotor function could significantly alter the non-reflex component of spastic hypertonia. Further research needs to investigate how the fusimotor activation changes the non-reflex component of passive resistance in spastic muscles.

Limitations of this study include the number of stretch measurements made at each thermal condition. The muscle reflex response is highly variable, but also typically shows a decrease in amplitude with each successive stretch within a short period of time. Only two measurements were made in each thermal condition as to not heavily weigh whichever condition was measured first. This potential bias was also remediated by randomizing the order of the thermal condition. Thermal stimulation was applied only to the contralateral side in this study. The effect of thermal stimulation would be more significant if it was applied on the same side or directly on the target muscles. However, the potential confounding factor is that increased passive stiffness could be induced directly by cold stimulation. In future studies, comparisons of the effects of thermal stimulation to the spastic muscles and on the contralateral side may be able to provide useful information.

The findings provide objective evidence for anecdotal clinical observations of increased muscle spasticity due to cold exposure. Increased spastic hypertonia appears to be primarily caused by an alteration in the non-reflex component of spastic hypertonia at a central level.

The experiment was approved by a local Institutional Review Board.

SL, HS, PZ, and XL: study concept and design; analysis and interpretation; critical revision of the manuscript for important intellectual content. HS and XL: acquisition of data. SL: study supervision.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.